This paper aims to illustrate how combining multiple approaches can inform us about the neurobiology of ADHD. Converging evidence from genetic, psychopharmacological and functional neuroimagingstudies has implicated dopaminergic fronto-striatal circuitry in ADHD. However, while the observation of converging evidence from multiple vantage points…

This review presents the most recent research concerning neuroimaging in developmental disabilities. Changes in structure and activation have been found in children with ADHD and learning disabilities, following intervention. For the children with learning disabilities changes in activation have been found following intensive behavioral and…

Use of estrogen therapy in the perimenopausal and postmenopausal periods has been shown in several clinical trials to help women maintain a premenopausal level of cognitive function. What is not yet fully understood is how the neurobiological effects of estrogen contribute to these cognitive effects. This review explores data from two related bodies of human literature that provide compelling evidence in support of the biological plausibility that estrogen treatment can benefit cognition. The first half of the literature review focuses on studies from the estrogen neuroimaging literature, and the second half focuses on pharmacologic challenge studies assessing estrogen-neurotransmitter interactions. We integrate these two bodies of literature by focusing on the neurophysiologic underpinnings of estrogen effects on cognition and linking these clinical studies to preclinical studies. The focus on verbal memory is important because it is a cognitive function that has been shown to change with estrogen treatment and predict Alzheimer's disease risk but is not addressed by preclinical studies. Overall, we conclude that estrogen interacts with cholinergic and serotonergic systems to affect hippocampal and frontal cortical brain areas and thereby enhance memory, particularly at the retrieval stage.

Functional Magnetic Resonance Imaging (fMRI) is an effective tool for identifying brain areas and networks implicated in human timing. But fMRI is not just a phrenological tool: by careful design, fMRI can be used to disentangle discrete components of a timing task and control for the underlying cognitive processes (e.g. sustained attention and WM updating) that are critical for estimating stimulus duration in the range of hundreds of milliseconds to seconds. Moreover, the use of parametric designs and correlational analyses allows us to better understand not just where, but also how, the brain processes temporal information. In addition, by combining fMRI with psychopharmacological manipulation, we can begin to uncover the complex relationship between cognition, neurochemistry and anatomy in the healthy human brain. This chapter provides an overview of some of the key findings in the functional imaging literature of both duration estimation and temporal prediction, and outlines techniques that can be used to allow timing-related activations to be interpreted more unambiguously. In our own studies, we have found that estimating event duration, whether that estimate is provided by a motor response or a perceptual discrimination, typically recruits basal ganglia, SMA and right inferior frontal cortex, and can be modulated by dopaminergic activity in these areas. By contrast, orienting attention to predictable moments in time in order to optimize behaviour, whether that is to speed motor responding or improve perceptual accuracy, recruits left inferior parietal cortex.

Hypotheses may be generated (and conclusions drawn) from observational studies in areas where information from randomized controlled trials (RCTs) is unavailable. However, observational studies can only establish that significant associations exist between predictor and outcome variables. Observational studies cannot establish that the associations identified represent cause-and-effect relationships. This article discusses examples of associations that were identified in observational studies and that were subsequently refuted in RCTs. Examples are also provided of associations that have yet to be confirmed or refuted but that are nevertheless influential in psychopharmacologic practice. Explanations are offered about how confounding might explain significant relationships between variables that are not related by cause and effect. As a conclusion of this exercise, clinicians are cautioned against placing too much reliance on the findings of observational research.

A growing body of evidence suggests that psychiatric medication outcomes are shaped significantly by psychological and social factors surrounding the prescribing process. Little, however, is known about the extent to which psychiatry programs integrate this evidence base into residency training or the methods by which this is accomplished. Psychiatry residency program directors and chief residents participated in an exploratory online survey to establish how psychosocial factors known to impact medication outcomes are integrated into psychopharmacology education. While participants highly valued the importance of psychosocial factors in the prescribing process, there was limited emphasis of these factors in psychopharmacology training. Additionally, some teaching methods that could advance understanding of complex interactions in the psychopharmacology relationship were found to be underutilized. Given that medication outcomes are significantly influenced by psychosocial factors, psychiatric educators have a responsibility to teach residents about the evidence base available. Residents exposed to this evidence base will be better equipped to manage the complexities of the psychopharmacology role. The results of this study offer clues as to how psychosocial factors may be more fully integrated into residency psychopharmacology training.

Impaired social cognition is considered a core contributor to unfavorable psychosocial functioning in schizophrenia. Rather than being a unitary process, social cognition is a collection of multifaceted processes that recruit multiple brain structures, thus structural and functional neuroimaging techniques are ideal methodologies for revealing the underlying pathophysiology of impaired social cognition. Many neuroimagingstudies have suggested that in addition to white-matter deficits, schizophrenia is associated with decreased gray-matter volume in multiple brain areas, especially fronto-temporal and limbic regions. However, few schizophrenia studies have examined associations between brain abnormalities and social cognitive disabilities. During the last decade, we have investigated structural brain abnormalities in schizophrenia using high-resolution magnetic resonance imaging, and our findings have been confirmed by us and others. By assessing different types of social cognitive abilities, structural abnormalities in multiple brain regions have been found to be associated with disabilities in social cognition, such as recognition of facial emotion, theory of mind, and empathy. These structural deficits have also been associated with alexithymia and quality of life in ways that are closely related to the social cognitive disabilities found in schizophrenia. Here, we overview a series of neuroimagingstudies from our laboratory that exemplify current research into this topic, and discuss how it can be further tackled using recent advances in neuroimaging technology.

(--)-Nuciferine and its Hofmann degradation product atherosperminine showed divergent psychopharmacological effects. Because nuciferine has been reported to be a neuroleptic and atherosperminine has some chemical resemblance to dopamine, they were investigated for their dopamine-receptor activities. Nuciferine had a pharmacologic profile of action associated with dopamine-receptor blockade; i.e., it induced catalepsy, inhibited spontaneous motor activity, conditioned avoidance response, amphetamine toxicity and stereotypy. On the other hand, atherosperminine produced effects associated with dopamine receptor stimulation, i.e., stereotypy, increase in spontaneous motor activity and amphetamine toxicity, reversal of haloperidol-induced catalepsy and inhibition of conditioned avoidance response, inhibition of morphine analgesia, and potentiation of the anticonvulsant action of diphenylhydantoin. The results are discussed on the basis of the chemical configuration of the two compounds.

The renewal of the philosophical debate in psychiatry is one exciting news of recent years. However, its use in psychopharmacology may be problematic, ranging from self-confinement into the realm of values (which leaves the evidence-based domain unchallenged) to complete rejection of scientific evidence. In this paper philosophy is conceived as a conceptual audit of clinical psychopharmacology. Its function is to criticise the epistemological and methodological problems of current neopositivist, ingenuously realist and evidence-servant psychiatry from within the scientific stance and with the aim of aiding psychopharmacologists in practicing a more self-aware, critical and possibly useful clinical practice. Three examples are discussed to suggest that psychopharmacological practice needs conceptual clarification. At the diagnostic level it is shown that the crisis of the current diagnostic system and the problem of comorbidity strongly influence psychopharmacological results, new conceptualizations more respondent to the psychopharmacological requirements being needed. Heterogeneity of research samples, lack of specificity of psychotropic drugs, difficult generalizability of results, need of a phenomenological study of drug-induced psychopathological changes are discussed herein. At the methodological level the merits and limits of evidence-based practice are considered, arguing that clinicians should know the best available evidence but that guidelines should not be constrictive (due to several methodological biases and rhetorical tricks of which the clinician should be aware, sometimes respondent to extra-scientific, economical requests). At the epistemological level it is shown that the clinical stance is shaped by implicit philosophical beliefs about the mind/body problem (reductionism, dualism, interactionism, pragmatism), and that philosophy can aid physicians to be more aware of their beliefs in order to choose the most useful view and to practice coherently

Experience sampling methods (ESM) and ecological momentary assessment (EMA) offer insight into daily life experiences, including symptoms of mental disorders. The application of ESM/EMA in psychopharmacology can be a valuable addition to more traditional measures such as retrospective self-report questionnaires because they may help reveal the impact of psychotropic medication on patients' actual experiences. In this paper we systematically review the existing literature on the use of ESM/EMA in psychopharmacology research. To this end, we searched the PsycInfo and Medline databases for all available ESM/EMA studies on the use of psychotropic medication in patients with DSM-III-R and DSM-IV disorders. Dissertations were excluded. We included 18 studies that applied ESM/EMA to study the effects of medication on patients with major depressive disorder, substance use disorder, attention-deficit hyperactivity disorder, psychotic disorder, and anxiety disorder. We found that ESM/EMA may allow researchers and clinicians to track patients during different phases of treatment: before treatment to predict outcome, during treatment to examine the effects of treatment on symptoms and different aspects of daily life experience, and after treatment to detect vulnerability for relapse. Moreover, ESM/EMA can potentially help determine how long and in what contexts medications are effective. Thus, ESM/EMA may benefit both researchers and clinicians and might prove to be an effective tool for improving the treatment of psychiatric patients.

The use of longitudinal neuroimaging to study the developmental perspectives of brain pathology in children with childhood-onset schizophrenia (COS) is described. Structural neuroimaging is capable of providing evidence of neurobiological specificity of COS to distinguish it from other brain abnormalities seen in neuropsychiatric illnesses like…

The current review gives an overview of brain studies in transgender people. First, we describe studies into the aetiology of feelings of gender incongruence, primarily addressing the sexual differentiation hypothesis: does the brain of transgender individuals resemble that of their natal sex, or that of their experienced gender? Findings from neuroimagingstudies focusing on brain structure suggest that the brain phenotypes of trans women (MtF) and trans men (FtM) differ in various ways from control men and women with feminine, masculine, demasculinized and defeminized features. The brain phenotypes of people with feelings of gender incongruence may help us to figure out whether sex differentiation of the brain is atypical in these individuals, and shed light on gender identity development. Task-related imaging studies may show whether brain activation and task performance in transgender people is sex-atypical. Second, we review studies that evaluate the effects of cross-sex hormone treatment on the brain. This type of research provides knowledge on how changes in sex hormone levels may affect brain structure and function.

Deep learning methods have recently made notable advances in the tasks of classification and representation learning. These tasks are important for brain imaging and neuroscience discovery, making the methods attractive for porting to a neuroimager's toolbox. Success of these methods is, in part, explained by the flexibility of deep learning models. However, this flexibility makes the process of porting to new areas a difficult parameter optimization problem. In this work we demonstrate our results (and feasible parameter ranges) in application of deep learning methods to structural and functional brain imaging data. These methods include deep belief networks and their building block the restricted Boltzmann machine. We also describe a novel constraint-based approach to visualizing high dimensional data. We use it to analyze the effect of parameter choices on data transformations. Our results show that deep learning methods are able to learn physiologically important representations and detect latent relations in neuroimaging data.

Obsessive compulsive disorder (OCD) is a relatively common psychiatric illness with a lifetime prevalence of 2–3% in general population. The pathophysiology of OCD is not yet fully understood, however over the last few decades, evidence for abnormalities of cortico-striatal-thalamic-cortico (CSTC) circuitry in etiopathogenesis of OCD has accumulated. Recent brain imaging techniques have been particularly convincing in suggesting that CSTC circuits are responsible for mediation of OCD symptoms. Neuroimagingstudies, especially more recent studies using functional neuroimaging methods have looked for possible changes seen in the brain of patients with OCD, the specificity of the findings (as compared to other psychiatric illnesses) and the effects of treatment (pharmacotherapy/psychotherapy) on such changes were observed. This narrative review discusses the neuroimaging findings seen in patients with OCD with a special focus on relatively more recent neuroimaging modalities such as magnetic resonance spectroscopy and magnetoencephalography. PMID:27833219

It has been long established that psychological interventions can markedly alter patients' thinking patterns, beliefs, attitudes, emotional states, and behaviors. Little was known about the neural mechanisms mediating such alterations before the advent of functional neuroimaging techniques. Since the turn of the new millenium, several functional neuroimagingstudies have been conducted to tackle this important issue. Some of these studies have explored the neural impact of various forms of psychotherapy in individuals with major depressive disorder. Other neuroimagingstudies have investigated the effects of psychological interventions for anxiety disorders. I review these studies in the present article, and discuss the putative neural mechanisms of change in psychotherapy. The findings of these studies suggest that mental and behavioral changes occurring during psychotherapeutic interventions can lead to a normalization of functional brain activity at a global level.

There is little doubt that undergraduate and post-graduate training of physicians, pharmacists, and nurses is insufficient to prepare them to use psychotropics safely and effectively, especially in the context of their expanded off-label uses. Therefore, the development of competencies in psychotropic prescribing needs to be approached as a long-term, practice-based learning commitment. Proposed are the abilities and knowledge components necessary for safe and effective use of psychotropics. Typical challenges in prescribing for chronic and recurrent illnesses include highly variable responses and tolerability, drug interactions, and adverse effects that can be serious, irreversible, and even fatal. Prescribing psychotropics is further complicated by negative public and professional reports and growing patient concerns about the quality of care, and questions about the efficacy, safety, and addictive risks of psychotropics. Increased efforts are needed to enhance clinical training and knowledge in psychopharmacology among trainees and practising clinicians, with more comprehensive and sustained attention to the assessment of individual patients, and greater reliance on patient education and collaboration. Improved competence in psychotropic prescribing should lead to more informed, thoughtful, and better-targeted applications as one component of more comprehensive clinical care.

Objective: As part of an effort to improve psychopharmacology training in psychiatric residency programs, a committee of residency training directors and associate directors adapted an introductory schizophrenia presentation from the American Society of Clinical Psychopharmacology's Model Psychopharmacology Curriculum to develop a multimodal,…

Magnetoencephalography (MEG) is a neuroimaging technique that allows direct measurement of the magnetic fields generated by synchronised ionic neural currents in the brain with moderately good spatial resolution and high temporal resolution. Because chemical neuromodulation can cause changes in neuronal processing on the millisecond time-scale, the combination of MEG with pharmacological interventions (pharmaco-MEG) is a powerful tool for measuring the effects of experimental modulations of neurotransmission in the living human brain. Importantly, pharmaco-MEG can be used in both healthy humans to understand normal brain function and in patients to understand brain pathologies and drug-treatment effects. In this paper, the physiological and technical basis of pharmaco-MEG is introduced and contrasted with other pharmacological neuroimaging techniques. Ongoing developments in MEG analysis techniques such as source-localisation, functional and effective connectivity analyses, which have allowed for more powerful inferences to be made with recent pharmaco-MEG data, are described. Studies which have utilised pharmaco-MEG across a range of neurotransmitter systems (GABA, glutamate, acetylcholine, dopamine and serotonin) are reviewed.

Introduction While pain in multiple sclerosis (MS) is common, in many cases the precise mechanisms are unclear. Neuroimagingstudies could have a valuable role in investigating the aetiology of pain syndromes. The aim of this review was to synthesise and appraise the current literature on neuroimagingstudies of pain syndromes in MS. Methods We systematically searched PubMed and Scopus from their inception dates to the 2nd of April 2013. Studies were selected by predefined inclusion and exclusion criteria. Methodological quality was appraised. Descriptive statistical analysis was conducted. Results We identified 38 studies of variable methodology and quality. All studies but one used conventional structural magnetic resonance imaging, and the majority reported a positive association between location of demyelinating lesions and specific neuropathic pain syndromes. Most investigated headache and facial pain, with more common pain syndromes such as limb pain being relatively understudied. We identified a number of methodological concerns, which along with variable study design and reporting limit our ability to synthesise data. Higher quality studies were however less likely to report positive associations of lesion distribution to pain syndromes. Conclusions Further high quality hypothesis-driven neuroimagingstudies of pain syndromes in MS are required to clarify pain mechanisms, particularly for the commonest pain syndromes. PMID:25161898

Hypnosis modulates pain perception and tolerance by affecting cortical and subcortical activity in brain regions involved in these processes. By reviewing functional neuroimagingstudies focusing on pain perception under hypnosis, the authors aimed to identify brain activation-deactivation patterns occurring in hypnosis-modulated pain conditions. Different changes in brain functionality occurred throughout all components of the pain network and other brain areas. The anterior cingulate cortex appears to be central in modulating pain circuitry activity under hypnosis. Most studies also showed that the neural functions of the prefrontal, insular, and somatosensory cortices are consistently modified during hypnosis-modulated pain conditions. Functional neuroimagingstudies support the clinical use of hypnosis in the management of pain conditions.

Although sleep is a familiar phenomenon, its functions are yet to be elucidated. Understanding these functions of sleep is an important focus area in neuroscience. Electroencephalography (EEG) has been the predominantly used method in human sleep research but does not provide detailed spatial information about brain activation during sleep. To supplement the spatial information provided by this method, researchers have started using a combination of EEG and various advanced neuroimaging techniques that have been recently developed, including positron emission tomography (PET) and magnetic resonance imaging (MRI). In this paper, we will review the recent progress in sleep studies, especially studies that have used such advanced neuroimaging techniques. First, we will briefly introduce several neuroimaging techniques available for use in sleep studies. Next, we will review the spatiotemporal brain activation patterns during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep, the dynamics of functional connectivity during sleep, and the consolidation of learning and memory during sleep; studies on the neural correlates of dreams, which have not yet been identified, will also be discussed. Lastly, possible directions for future research in this area will be discussed.

In the past two decades, neuroimaging investigations of stuttering have led to important discoveries of structural and functional brain differences in people who stutter, providing significant clues to the neurological basis of stuttering. One major limitation, however, has been that most studies so far have only examined adults who stutter, whose brain and behavior likely would have adopted compensatory reactions to their stuttering; these confounding factors have made interpretations of the findings difficult. Developmental stuttering is a neurodevelopmental condition, and like many other neurodevelopmental disorders, stuttering is associated with an early childhood onset of symptoms and greater incidence in males relative to females. More recent studies have begun to examine children who stutter using various neuroimaging techniques that allow examination of functional neuroanatomy and interaction of major brain areas that differentiate children who stutter compared with age-matched controls. In this article, I review these more recent neuroimaging investigations of children who stutter, in the context of what we know about typical brain development, neuroplasticity, and sex differences relevant to speech and language development. Although the picture is still far from complete, these studies have potential to provide information that can be used as early objective markers, or prognostic indicators, for persistent stuttering in the future. Furthermore, these studies are the first steps in finding potential neural targets for novel therapies that may involve modulating neuroplastic growth conducive to developing and maintaining fluent speech, which can be applied to treatment of young children who stutter.

Over the past decade, brain imaging has helped to better define eating disorder-related brain circuitry. Brain research on gray matter (GM) and white matter (WM) volumes had been inconsistent, possibly due to the effects of acute starvation, exercise, medication, and comorbidity, but newer studies have controlled for such effects. Those studies suggest larger left medial orbitofrontal gyrus rectus volume in ill adult and adolescent anorexia nervosa after recovery from anorexia nervosa, and in adult bulimia nervosa. The orbitofrontal cortex is important in terminating food intake, and altered function could contribute to self-starvation. The right insula, which processes taste but also interoception, was enlarged in ill adult and adolescent anorexia nervosa, as well as adults recovered from the illness. The fixed perception of being fat in anorexia nervosa could be related to altered insula function. A few studies investigated WM integrity, with the most consistent finding of reduced fornix integrity in anorexia and bulimia nervosa-a limbic pathway that is important in emotion but also food intake regulation. Functional brain imaging using basic sweet taste stimuli in eating disorders during the ill state or after recovery implicated repeatedly reward pathways, including insula and striatum. Brain imaging that targeted dopamine-related brain activity using taste-reward conditioning tasks suggested that this circuitry is hypersensitive in anorexia nervosa, but hyporesponsive in bulimia nervosa and obesity. Those results are in line with basic research and suggest adaptive reward system changes in the human brain in response to extremes of food intake-changes that could interfere with normalization of eating behavior.

Imaging genetics is an emerging methodology that combines genetic information with imaging-derived metrics to understand how genetic factors impact observable structural, functional, and quantitative phenotypes. Many of the most well-known genetic studies are based on Genome-Wide Association Studies (GWAS), which use large populations of related or unrelated individuals to associate traits and disorders with individual genetic factors. Merging imaging and genetics may potentially lead to improved power of association in GWAS because imaging traits may be more sensitive phenotypes, being closer to underlying genetic mechanisms, and their quantitative nature inherently increases power. We are developing SOLAR-ECLIPSE (SE) imaging genetics software which is capable of performing genetic analyses with both large-scale quantitative trait data and family structures of variable complexity. This program can estimate the contribution of genetic commonality among related subjects to a given phenotype, and essentially answer the question of whether or not the phenotype is heritable. This central factor of interest, heritability, offers bounds on the direct genetic influence over observed phenotypes. In order for a trait to be a good phenotype for GWAS, it must be heritable: at least some proportion of its variance must be due to genetic influences. A variety of family structures are commonly used for estimating heritability, yet the variability and biases for each as a function of the sample size are unknown. Herein, we investigate the ability of SOLAR to accurately estimate heritability models based on imaging data simulated using Monte Carlo methods implemented in R. We characterize the bias and the variability of heritability estimates from SOLAR as a function of sample size and pedigree structure (including twins, nuclear families, and nuclear families with grandparents).

This editorial provides a summary of the highlights from 11 new papers that have been published in a special issue of Brain and Language on the neurobiology of reading. The topics investigate reading mechanisms in both adults and children. Several of the findings illustrate how responses in the left ventral occipito-temporal cortex, and other reading areas, change with learning, expertise and the task: In the early stages of reading acquisition, learning/expertise increases activation in reading areas as well as in an attentionally-controlled, learning circuit. In later stages, expertise and efficiency decrease activation within the reading network and increase anatomical connectivity. Special interest is given to a white matter tract (the vertical occipital fasciculus) that projects dorsally from the left occipito-temporal cortex to the posterior parietal lobe. This observation fits with a magnetoencephalography study showing how activity in the angular gyrus is influenced by early occipito-temporal activity; with angular gyrus activity contributing to inferior frontal activity. Overall, the papers within the special issue illustrate the wide range of different techniques that can be used to reveal the functional anatomy of reading and the time course of activity within the different reading pathways.

A critical examination of speech motor control depends on an in-depth understanding of network connectivity associated with Brodmann areas 44 and 45 and surrounding cortices. Damage to these areas has been associated with two conditions—the speech motor programming disorder apraxia of speech (AOS) and the linguistic/grammatical disorder of Broca’s aphasia. Here we focus on AOS, which is most commonly associated with damage to posterior Broca’s area (BA) and adjacent cortex. We provide an overview of our own studies into the nature of AOS, including behavioral and neuroimaging methods, to explore components of the speech motor network that are associated with normal and disordered speech motor programming in AOS. Behavioral, neuroimaging, and computational modeling studies are indicating that AOS is associated with impairment in learning feedforward models and/or implementing feedback mechanisms and with the functional contribution of BA6. While functional connectivity methods are not yet routinely applied to the study of AOS, we highlight the need for focusing on the functional impact of localized lesions throughout the speech network, as well as larger scale comparative studies to distinguish the unique behavioral and neurological signature of AOS. By coupling these methods with neural network models, we have a powerful set of tools to improve our understanding of the neural mechanisms that underlie AOS, and speech production generally. PMID:25404911

The role of experimental psychology in the development of psychopharmacology has largely been ignored in recent historical accounts. In this article the authors attempt to redress that gap by outlining work in early experimental psychology that contributed significantly to the field. While psychiatrists focused on the therapeutic nature of drugs or their mimicry of psychopathology, experimental psychologists used psychoactive drugs as tools to study individual differences in normal behavior as well as to develop methodologies using behavior to study mechanisms of drug action. Experimental work by Kraepelin, Rivers, and Hollingworth was particularly important in establishing drug-screening protocols still used today. Research on nitrous oxide and on the effects of drug combinations is discussed to illustrate the importance of experimental psychology to psychopharmacology.

In this article, we reviewed brain damage seen in patients with alcohol dependence briefly focusing on neuroimagingstudies. In uncomplicated alcoholic patients, a high incidence of cortical shrinkage and ventricular dilatation were reported using brain CT scans. In older alcoholics, prefrontal gray matter deficits were especially marked when compared with younger alcoholics. Reversibility of brain shrinkage is a common neuroimaging finding in patients with alcohol dependence and a study by Gazdinski et al. reported more rapid brain tissue gain during the first month of sobriety than in the following months. Another MRI study using deformation-based morphometry revealed significant shrinkage in the frontal and temporal lobes within 1 week of abstinence of alcoholic patients. This study followed participants for 8 months longitudinally and revealed that abstaining alcoholics recovered tissue volumes significantly faster than nonalcoholic controls in the parietal and frontal lobes and this study also revealed that when abstaining alcoholics were compared with relapsed alcoholics, additional regions with significantly greater recovery in abstainers were the temporal lobes, thalamus, brainstem, cerebellum, corpus callosum, anterior cingulate, insula, and subcortical white matter. Finally we introduced a MR spectroscopy (MRS) study on alcoholic patients. This study using proton MRS indicated that with short-term abstinence, cerebellar choline and frontomesial N-acetylaspartate (NAA) were significantly increased. Findings showing that a cerebellar choline increase and a frontomesial NAA increase were detected at stable water integrals and creatine concentrations, serum electrolytes and red blood cell indices suggest that early brain recovery through abstinence does not simply reflect rehydration. This might indicate that even the adult brain has capacities for regrowth and further understanding of the mechanisms of recovery of alcoholics' brains may result in a valuable

In recent years a gradual shift in the definition of Parkinson's disease (PD) has been established, from a classical akinetic-rigid movement disorder to a multi-system neurodegenerative disease. While the pathophysiology of PD is complex and goes much beyond the nigro-striatal degeneration, the striatum has been shown to be responsible for many cognitive functions. Patients with PD develop impairments in multiple cognitive domains and the PD model is probably the most extensively studied regarding striatum dysfunction and its influence on cognition. Up to 40% of PD patients present cognitive impairment even in the early stages of disease development. Thus, understanding the key patterns of striatum and connecting regions' influence on cognition will help develop more specific approaches to alleviate cognitive impairment and slow down its decline. This review focuses on the contribution of neuroimagingstudies in understanding how striatum impairment affects cognition in PD. PMID:26500512

Presents basic information on psychopharmacology and discusses the major antipsychotic, antidepressant, anti-anxiety, and lithium salt medications used with adults. The importance and implications of psychopharmacology for the counseling profession are highlighted. (Author)

Objective: To describe our experience of learning clinical psychopharmacology during residency, in order to assist educators planning psychopharmacology curricula. Methods: We describe how psychopharmacology teaching was structured in our program, dividing our experience into two phases, early residency (PGY-I and PGY-II) and late residency…

Autism is a neurobiological disorder. The core clinical features of autism include impairment in social interaction, impairments in verbal and nonverbal communication, and restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. Autism often has coexisting neuropsychiatric disorders, including seizure disorders, attention deficit hyperactivity disorder, affective disorders, anxiety disorder, obsessive-compulsive disorder, and Tourette disorder. No etiology-based treatment modality has been developed to cure individuals with autism. However, comprehensive intervention, including parental counseling, behavior modification, special education in a highly structured environment, sensory integration training, speech therapy, social skill training, and medication, has demonstrated significant treatment effects in many individuals with autism. Findings from preliminary studies of major neurotransmitters and other neurochemical agents strongly suggest that neurochemical factors play a major role in autism. The findings also provide the rationale for psychopharmacotherapy in individuals with autism. This article reviews studies of neurochemical systems and related psychopharmacological research in autism and related neuropsychiatric disorders. Clinical indications for pharmacotherapy are described, and uses of various medications are suggested. This article also discusses new avenues of investigation that may lead to the development of more effective medication treatments in persons with autism.

Using neuroimaging techniques to explore the central mechanism of acupuncture gains increasing attention, but the quality control of acupuncture-neuroimagingstudy remains to be improved. We searched the PubMed Database during 1995 to 2014. The original English articles with neuroimaging scan performed on human beings were included. The data involved quality control including the author, sample size, characteristics of the participant, neuroimaging technology, and acupuncture intervention were extracted and analyzed. The rigorous inclusion and exclusion criteria are important guaranty for the participants' homogeneity. The standard operation process of acupuncture and the stricter requirement for acupuncturist play significant role in quality control. More attention should be paid to the quality control in future studies to improve the reproducibility and reliability of the acupuncture-neuroimagingstudies. PMID:27242911

Educational neuroscience is an emerging scientific field that brings together researchers from neuroscience, psychology, and education to explore the neurocognitive processes underlying educational practice and theory. In this brief article, we take reading disorder (RD, also known as developmental dyslexia) as an example, and explore trends in neuroimaging research, which may have future implications for educational practice and policy. Specifically, we present two examples that have been central to research efforts in our laboratory: (a) utilizing multimodal neuroimaging to optimize criteria to diagnose RD, and (b) identifying neuroimaging markers that predict future academic outcomes. Such research is faced with important challenges, and rigorous validation is necessary before any claims of the widespread practical utility of neuroimaging can be made. Nevertheless, we contend that neuroimagingstudies offer opportunities for providing critical information that could lead to advancing theory of reading and RD. This could in turn lead to better diagnostic criteria and more accurate and earlier identification of RD. PMID:25732015

Patients experiencing mental disorders are at an elevated risk for developing aggressive behavior. In the past 10 years, the psychopharmacological treatment of aggression has changed dramatically owing to the introduction of atypical antipsychotics on the market and the increased use of anticonvulsants and lithium in the treatment of aggressive patients.This review (second of 2 parts) uses a translational medicine approach to examine the neurobiology of aggression, discussing the major neurotransmitter systems implicated in its pathogenesis (serotonin, glutamate, norepinephrine, dopamine, and γ-aminobutyric acid) and the neuropharmacological rationale for using atypical antipsychotics, anticonvulsants, and lithium in the therapeutics of aggressive behavior. A critical review of all clinical trials using atypical antipsychotics (aripiprazole, clozapine, loxapine, olanzapine, quetiapine, risperidone, ziprasidone, and amisulpride), anticonvulsants (topiramate, valproate, lamotrigine, and gabapentin), and lithium are presented. Given the complex, multifaceted nature of aggression, a multifunctional combined therapy, targeting different receptors, seems to be the best strategy for treating aggressive behavior. This therapeutic strategy is supported by translational studies and a few human studies, even if additional randomized, double-blind, clinical trials are needed to confirm the clinical efficacy of this framework.

Neuroimagingstudies have produced seemingly contradictory findings in regards to the pathophysiology of insomnia. Although most study results are interpreted from the perspective of a “hyperarousal” model, the aggregate findings from neuroimagingstudies suggest a more complex model is needed. We provide a review of the major findings from neuroimagingstudies, then discuss them in relation to a heuristic model of sleep-wake states that involves three major factors: wake drive, sleep drive, and level of conscious awareness. We propose that insomnia involves dysregulation in these factors, resulting in subtle dysregulation of sleep-wake states throughout the 24 h light/dark cycle. PMID:28241468

Although there are a number of statistical software tools for voxel-based massively univariate analysis of neuroimaging data, such as fMRI (functional MRI), PET (positron emission tomography), and VBM (voxel-based morphometry), very few software tools exist for power and sample size calculation for neuroimagingstudies. Unlike typical biomedical studies, outcomes from neuroimagingstudies are 3D images of correlated voxels, requiring a correction for massive multiple comparisons. Thus, a specialized power calculation tool is needed for planning neuroimagingstudies. To facilitate this process, we developed a software tool specifically designed for neuroimaging data. The software tool, called PowerMap, implements theoretical power calculation algorithms based on non-central random field theory. It can also calculate power for statistical analyses with FDR (false discovery rate) corrections. This GUI (graphical user interface)-based tool enables neuroimaging researchers without advanced knowledge in imaging statistics to calculate power and sample size in the form of 3D images. In this paper, we provide an overview of the statistical framework behind the PowerMap tool. Three worked examples are also provided, a regression analysis, an ANOVA (analysis of variance), and a two-sample T-test, in order to demonstrate the study planning process with PowerMap. We envision that PowerMap will be a great aide for future neuroimaging research.

The marketing of selective serotonin reuptake inhibitors in the psychopharmacological industry presents a serious moral problem for the corporate model of medicine. In this paper I examine ethical issues relating to the efficacy and safety of these drugs. Pharmaceutical companies have a moral obligation to disclose all information in their possession bearing on the true risks and benefits of their drugs. Only then can patients make fully informed decisions about their treatment.

Reviewed on a layman's level was research on psychopharmacology with the emotionally and behaviorally disturbed. General conclusions drawn from the man y studies were that the effect of drugs on intellectual functioning had not been determined and that there was little evidence to indicate that the learning process was consistently and reliably…

The development of geriatric psychopharmacology was built on advances in geriatric psychiatry nosology and clinical pharmacology and on increased investment in aging research by the National Institute of Mental Health and by academic institutions. Application of the US Food and Drug Administration's geriatric labeling rule provided further impetus. Developments in the knowledge about 3 principal classes of medications (antidepressants, antipsychotics, and treatments for Alzheimer's disease) illustrate the trajectory of geriatric psychopharmacology research. Nonetheless, the loss of information about age effects that has resulted from applying age exclusion criteria in studies limited to either younger adults or geriatric patients is regrettable. Antidepressant trials have moved from studying younger and medically well "geriatric" samples to focusing on "older old" persons and those with significant medical comorbidity including coronary artery disease, cerebrovascular disease, and dementia. Increased specificity is reflected in studies of relationships between specific neuropsychological deficits, specific brain abnormalities, and antidepressant responsiveness. Clinical trials in older adults have demonstrated that the efficacy of antipsychotic medications continues across the lifespan, but that sensitivity to specific side effects changes in older age, with poor tolerability frequently mitigating the benefits of treatment. Treatments for Alzheimer's disease have fallen within the purview of geriatric psychopharmacology. The research focus is increasingly shifting from treatments to slow the course of cognitive decline to studies of early diagnosis and of interventions designed to prevent the development of deficits in vulnerable individuals. The importance of geriatric psychopharmacology will grow further as the average lifespan increases all over the world.

Individual differences in response to pharmacologic treatment limits the usefulness of mean data obtained from randomized controlled trials. These individual differences exist even in genetically uniform inbred mouse strains. While stratification can be of value in large studies, the individual patient history is the most effective currently available guide for personalized medicine in psychopharmacology.

Background: The characterization of the first episode of psychosis and how it should be treated are principal issues in actual research. Realistic, naturalistic studies are necessary to represent the entire population of first episode of psychosis attended in daily practice. Methods: Sixteen participating centers from the PEPs project recruited 335 first episode of psychosis patients, aged 7 to 35 years. This article describes and discusses the psychopharmacological interventions and safety profiles at baseline and during a 60-day pharmacovigilance period. Results: The majority of first episode of psychosis patients received a second-generation antipsychotic (96.3%), orally (95%), and in adjusted doses according to the product specifications (87.2%). A total of 24% were receiving an antipsychotic polytherapy pattern at baseline, frequently associated with lower or higher doses of antipsychotics than the recommended ones. Eight patients were taking clozapine, all in monotherapy. Males received higher doses of antipsychotic (P=.043). A total of 5.2% of the patients were being treated with long-acting injectable antipsychotics; 12.2% of the patients received anticholinergic drugs, 12.2% antidepressants, and 13.7% mood stabilizers, while almost 40% received benzodiazepines; and 35.52% reported at least one adverse drug reaction during the pharmacovigilance period, more frequently associated with higher antipsychotic doses and antipsychotic polytherapy (85.2% vs 45.5%, P

Objective: To review the current status of psychopharmacology education for medical students, residents, and practitioners in psychiatry and other specialties. Methods: A search of the MEDLINE and PsychInfo data bases was conducted using four keywords: pharmacology, psychopharmacology, teaching, and student. Additional references were obtained…

Increased manganese (Mn) exposure is known to cause cognitive, psychiatric and motor deficits. Mn exposure occurs in different occupational settings, where the airborne Mn level and the size of respirable particulates may vary considerably. Recently the importance of the role of the cerebral cortex in Mn toxicity has been highlighted, especially in Mn-induced neuropsychological effects. In this study we used magnetic resonance imaging (MRI) to evaluate brain Mn accumulation using T1 signal intensity indices and to examine changes in brain iron content using T2* contrast, as well as magnetic resonance spectroscopy (MRS) to measure exposure-induced metabolite changes non-invasively in cortical and deep brain regions in Mn-exposed welders, Mn-exposed smelter workers and control factory workers with no measurable exposure to Mn. MRS data as well as T1 signal intensity indices and T2* values were acquired from the frontal cortex, posterior cingulate cortex, hippocampus, and thalamus. Smelters were exposed to higher air Mn levels and had a longer duration of exposure, which was reflected in higher Mn levels in erythrocytes and urine than in welders. Nonetheless, welders had more significant metabolic differences compared to controls than did the smelter workers, especially in the frontal cortex. T1 hyperintensities in the globus pallidus were observed in both Mn-exposed groups, but only welders showed significantly higher thalamic and hippocampal T1 hyperintensities, as well as significantly reduced T2* values in the frontal cortex. Our results indicate that (1) the cerebral cortex, in particular the frontal cortex, is clearly involved in Mn neurotoxic effects and (2) in spite of the lower air Mn levels and shorter duration of exposure, welders exhibit more extensive neuroimaging changes compared to controls than smelters, including measurable deposition of Mn in more brain areas. These results indicate that the type of exposure (particulate sizes, dust versus fume) and

The employment of neuroimagingstudies in the evaluation of individuals with developmental delay/mental retardation (DD/MR) is still highly debated. The Consensus Conference of the American College of Medical Genetics has suggested that "neuroimaging appears to have an especially important role in patients with microcephaly or macrocephaly, seizures, loss of psychomotor skills and neurologic signs," whereas the value of neuroimaging investigations "in the normocephalic patient without focal neurological signs is unclear" [Curry et al., 1997]. However, recent literature reports show how the latest neuroimaging techniques (in vivo proton magnetic resonance spectroscopy [H-MRS]) may prove to be useful in the diagnostic process of those individuals with DD/MR and no neurological signs/symptoms. The use of these techniques can, in addition, help in monitoring treatment in distinct metabolic disorders. This review will focus on the usefulness of neuroimagingstudies in some of the newer metabolic disorders. This paper will also cover those recognizable patterns of human malformation where neuroimaging findings seem to be relevant both toward diagnosis and management, and add to our understanding of the related behavior phenotype. The essential role of magnetic resonance imaging (MRI) on the progress in the diagnostic recognition of malformations of cerebral cortical development is stressed.

Research in psychopharmacology began around 1950 with the description of antipsychotic effect of chlorpromazine followed shortly later with the mechanism of action of antidepressants. In these initial phases, pharmacy industry was open to knowledge and made efforts tending to the development to new drugs that showed efficacy and good safety profiles. In parallel development of theories attempting to find the etiology of psychiatric disorders acquired impulse. This review summarizes the new drugs for the treatment of psychiatric disorders currently under development and also presents a short list of the main biomarkers proposed for the diagnosis or the comprehension of the etiopathogeny in Psychiatry. Several questions arose when brain structures, biochemical pathways, proteins and genes began to be identified in the search for a better comprehension of etiopathogeny of mental disorders. Pharmaceutical industry virtually moved away from this field of research. Epistemological and methodological obstacles in psychopharmacological investigation together with the lack of priority given by industry to this field allow us to predict few advances for the treatment in Psychiatry in the short term.

Background Mind-Body practices constitute a large and diverse group of practices that can substantially affect neurophysiology in both healthy individuals and those with various psychiatric disorders. In spite of the growing literature on the clinical and physiological effects of mind-body practices, very little is known about their impact on central nervous system (CNS) structure and function in adolescents with psychiatric disorders. Method This overview highlights findings in a select group of mind-body practices including yoga postures, yoga breathing techniques and meditation practices. Results Mind-body practices offer novel therapeutic approaches for adolescents with psychiatric disorders. Findings from these studies provide insights into the design and implementation of neuroimagingstudies for adolescents with psychiatric disorders. Conclusions Clinical neuroimagingstudies will be critical in understanding how different practices affect disease pathogenesis and symptomatology in adolescents. Neuroimaging of mind-body practices on adolescents with psychiatric disorders will certainly be an open and exciting area of investigation. PMID:27347478

The use of motivational interviewing strategies in the practice of adolescent psychopharmacology is described. Motivational interviewing is an efficient and collaborative style of clinical interaction and this helps adolescent patients to integrate their psychiatric difficulties into a more resilient identity.

This article reviews recent advances in the elucidation of neurobehavioral endophenotypes associated with drug addiction made possible by the translational neuroimaging techniques magnetic resonance imaging (MRI) and positron emission tomography (PET). Increasingly, these non-invasive imaging approaches have been the catalyst for advancing our understanding of the etiology of drug addiction as a brain disorder involving complex interactions between pre-disposing behavioral traits, environmental influences and neural perturbations arising from the chronic abuse of licit and illicit drugs. In this article we discuss the causal role of trait markers associated with impulsivity and novelty-/sensation-seeking in speeding the development of compulsive drug administration and in facilitating relapse. We also discuss the striking convergence of imaging findings from these behavioural traits and addiction in rats, monkeys and humans with a focus on biomarkers of dopamine neurotransmission, and highlight areas where further research is needed to disambiguate underlying causal mechanisms. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'.

Depression, anxiety, delirium, and other psychiatric symptoms are highly prevalent in the cancer setting, and pharmacological intervention is an important component in the overall psychosocial care of the patient. Psychopharmacology is also used as a primary or adjuvant treatment for the management of cancer-related symptoms stemming from the disease itself and/or its treatment, including sleep disturbance, loss of appetite, neuropathic pain, nausea, fatigue, and hot flashes. Psychiatrists, oncologists, and palliative care physicians working as members of a multidisciplinary team have the opportunity to target multiple symptoms that negatively affect a patient's quality of life with the strategic use of psychotropic medications when deemed appropriate. This article aims to review the indications for use of antidepressants, psychostimulants, anxiolytics, antipsychotics, and mood stabilizers in oncology. An updated review of the relevant literature is discussed and referenced in each section.

With the availability of new functional and structural neuroimaging techniques, researchers have begun to localize brain areas that may be dysfunctional in offenders who are aggressive and violent. Our review of 17 neuroimagingstudies reveals that the areas associated with aggressive and/or violent behavioral histories, particularly impulsive acts, are located in the prefrontal cortex and the medial temporal regions. These findings are explained in the context of negative emotion regulation, and suggestions are provided concerning how such findings may affect future theoretical frameworks in criminology, crime prevention efforts, and the functioning of the criminal justice system.

Convergent evidence implicates regional neural responses to reward anticipation in the pathogenesis of several psychiatric disorders, such as schizophrenia, where blunted ventral striatal responses to positive reward are observed in patients and at-risk populations. In vivo oxygen amperometry measurements in the ventral striatum in awake, behaving rats reveal reward-related tissue oxygen changes that closely parallel blood oxygen level dependent (BOLD) signal changes observed in human functional magnetic resonance imaging (fMRI), suggesting that a cross-species approach targeting this mechanism might be feasible in psychopharmacology. The present study explored modulatory effects of acute, subanaesthetic doses of ketamine—a pharmacological model widely used in psychopharmacological research, both preclinically and clinically—on ventral striatum activity during performance of a reward anticipation task in both species, using fMRI in humans and in vivo oxygen amperometry in rats. In a region-of-interest analysis conducted following a cross-over placebo and ketamine study in human subjects, an attenuated ventral striatal response during reward anticipation was observed following ketamine relative to placebo during performance of a monetary incentive delay task. In rats, a comparable attenuation of ventral striatal signal was found after ketamine challenge, relative to vehicle, in response to a conditioned stimulus that predicted delivery of reward. This study provides the first data in both species demonstrating an attenuating effect of acute ketamine on reward-related ventral striatal (O2) and fMRI signals. These findings may help elucidate a deeper mechanistic understanding of the potential role of ketamine as a model for psychosis, show that cross-species pharmacological experiments targeting reward signaling are feasible, and suggest this phenotype as a promising translational biomarker for the development of novel compounds, assessment of disease status, and

Modern computational neuroscience employs diverse software tools and multidisciplinary expertise to analyze heterogeneous brain data. The classical problems of gathering meaningful data, fitting specific models, and discovering appropriate analysis and visualization tools give way to a new class of computational challenges—management of large and incongruous data, integration and interoperability of computational resources, and data provenance. We designed, implemented and validated a new paradigm for addressing these challenges in the neuroimaging field. Our solution is based on the LONI Pipeline environment [3], [4], a graphical workflow environment for constructing and executing complex data processing protocols. We developed study-design, database and visual language programming functionalities within the LONI Pipeline that enable the construction of complete, elaborate and robust graphical workflows for analyzing neuroimaging and other data. These workflows facilitate open sharing and communication of data and metadata, concrete processing protocols, result validation, and study replication among different investigators and research groups. The LONI Pipeline features include distributed grid-enabled infrastructure, virtualized execution environment, efficient integration, data provenance, validation and distribution of new computational tools, automated data format conversion, and an intuitive graphical user interface. We demonstrate the new LONI Pipeline features using large scale neuroimagingstudies based on data from the International Consortium for Brain Mapping [5] and the Alzheimer's Disease Neuroimaging Initiative [6]. User guides, forums, instructions and downloads of the LONI Pipeline environment are available at http://pipeline.loni.ucla.edu. PMID:20927408

Neuropsychology and neuroimaging both provide information about the relationship between brain structure and function, and thus attempt to understand if the neural basis of cognition should benefit from converging results obtained across the two methods. However, serious attempts to integrate the two methodologies face several challenges, such as differences in basic paradigm designs. To illustrate these points, this article will review neuropsychological and neuroimaging research in the area of working memory. Points of discussion will include discrepancies between neuropsychological and neuroimaging evidence for domain-specific rehearsal systems, the role of left inferior parietal cortex in phonological storage, and the contributions of Brocas area and the cerebellum to articulatory rehearsal. Methodological factors and assumptions that may account for these discrepancies, and the steps that could be taken to overcome them, will be evaluated. The overall objective of this "case study" is to encourage neuroimagers and neuropsychologists to evaluate seriously the results obtained in both methodologies when formulating interpretations of their data and when designing new studies.

Background: Many studies have examined the timeliness of thrombolysis for acute ischemic stroke, but less is known about door-to-imaging time. We conducted a prospective cohort study to assess the timing of neuroimaging among patients with suspected acute stroke in the province of Ontario, Canada, and to examine factors associated with delays in neuroimaging. Methods: We included all patients 18 years and older with suspected acute stroke seen at hospitals with neuroimaging capacity within the Ontario Stroke Registry between Apr. 1, 2010, and Mar. 31, 2011. We used a hierarchical, multivariable Cox proportional hazards model to evaluate the association between patient and hospital factors and the likelihood of receiving timely neuroimaging (≤ 25 min) after arrival in the emergency department. Results: A total of 13 250 patients presented to an emergency department with stroke-like symptoms during the study period. Of the 3984 who arrived within 4 hours after symptom onset, 1087 (27.3%) had timely neuroimaging. The factors independently associated with an increased likelihood of timely neuroimaging were less time from symptom onset to presentation, more severe stroke, male sex, no history of stroke or transient ischemic attack, arrival to hospital from a setting other than home and presentation to a designated stroke centre or an urban hospital. Interpretation: A minority of patients with stroke-like symptoms who presented within the 4-hour thrombolytic treatment window received timely neuroimaging. Neuroimaging delays were influenced by various patient and hospital factors, some of which are modifiable. PMID:27398382

Selective serotonin reuptake inhibitors (SSRIs) are an efficacious and effective treatment for pediatric obsessive-compulsive disorder (OCD) but have received scrutiny due to a potential side effect constellation called activation syndrome. While recent research introduced a subjective measure of activation syndrome, objective measures have not been tested. This pilot study, using data from a larger randomized-controlled trial, investigated the potential of actigraphy to provide an objective measure of activation symptoms in 44 youths with OCD beginning an SSRI medication regimen. Data were collected over the first four weeks of a multisite, parallel, double-blind, randomized, placebo controlled psychopharmacological treatment study and statistical modeling was utilized to test how activation syndrome severity predicts daily and nightly activity levels. Results indicated that youths with higher activation symptoms had lower daytime activity levels when treatment averages were analyzed; in contrast youths who experienced onset of activation symptoms one week were more likely to have higher daytime and night-time activity ratings that week. Results support actigraphy as a potential objective measure of activation symptoms. Subsequent studies are needed to confirm these findings and test clinical applications for use by clinicians to monitor activation syndrome during SSRI treatment. National Institutes of Health (5UO1 MH078594-01); NCT00382291. PMID:25535011

Autism spectrum disorders (ASD) display significant heterogeneity. Although most neuroimagingstudies in ASD have been designed to identify commonalities among affected individuals, rather than differences, some studies have explored variation within ASD. There have been two general types of approaches used for this in the neuroimaging literature to date: comparison of subgroups within ASD, and analyses using dimensional measures to link clinical variation to brain differences. This review focuses on structural and functional magnetic resonance imaging studies that have used these approaches to begin to explore heterogeneity between individuals with ASD. Although this type of data is yet sparse, recognition is growing of the limitations of behaviorally defined categorical diagnoses for understanding neurobiology. Study designs that are more informative regarding the sources of heterogeneity in ASD have the potential to improve our understanding of the neurobiological processes underlying ASD. PMID:24198778

This article provides an overview of where psychiatric pharmacogenomic testing stands as an emerging clinical tool in modern psychotropic prescribing practice, specifically in the pediatric population. This practical discussion is organized around the state of psychiatric pharmacogenomics research when choosing psychopharmacologic interventions in the most commonly encountered mental illnesses in youth. As with the rest of the topics on psychopharmacology for children and adolescents in this publication, a clinical vignette is presented, this one highlighting a clinical case of a 16 year old genotyped during hospitalization for recalcitrant depression.

Paediatric psychopharmacology holds great promise in two equally important areas of enormous biomedical and social impact, namely the treatment of behavioural abnormalities in children and adolescents, and the prevention of psychiatric disorders with adolescent- or adult-onset. Yet, in striking contrast, pharmacological treatment options presently available in child and adolescent psychiatry are dramatically limited. The most important currently unmet needs in paediatric psychopharmacology are: the frequent off-label prescription of medications to children and adolescents based exclusively on data from randomized controlled studies involving adult patients; the frequent lack of age-specific dose, long-term efficacy and tolerability/safety data; the lack of effective medications for many paediatric psychiatric disorders, most critically autism spectrum disorder; the scarcity and limitations of randomized placebo-controlled trials in paediatric psychopharmacology; the unexplored potential for the prevention of psychiatric disorders with adolescent- and adult-onset; the current lack of biomarkers to predict treatment response and severe adverse effects; the need for better preclinical data to foster the successful development of novel drug therapies; and the effective dissemination of evidence-based treatments to the general public, to better inform patients and families of the benefits and risks of pharmacological interventions during development. Priorities and strategies are proposed to overcome some of these limitations, including the European Child and Adolescent Clinical Psychopharmacology Network, as an overarching Pan-European infrastructure aimed at reliably carrying out much needed psychopharmacological trials in children and adolescents, in order to fill the identified gaps and improve overall outcomes.

AIM To examine the effects of cognitive remediation therapies on brain functioning through neuroimaging procedures in patients with schizophrenia. METHODS A systematic, computerised literature search was conducted in the PubMed/Medline and PsychInfo databases. The search was performed through February 2016 without any restrictions on language or publication date. The search was performed using the following search terms: [(“cogniti*” and “remediation” or “training” or “enhancement”) and (“fMRI” or “MRI” or “PET” or “SPECT”) and (schizophrenia or schiz*)]. The search was accompanied by a manual online search and a review of the references from each of the papers selected, and those papers fulfilling our inclusion criteria were also included. RESULTS A total of 101 studies were found, but only 18 of them fulfilled the inclusion criteria. These studies indicated that cognitive remediation improves brain activation in neuroimagingstudies. The most commonly reported changes were those that involved the prefrontal and thalamic regions. Those findings are in agreement with the hypofrontality hypothesis, which proposes that frontal hypoactivation is the underlying mechanism of cognitive impairments in schizophrenia. Nonetheless, great heterogeneity among the studies was found. They presented different hypotheses, different results and different findings. The results of more recent studies interpreted cognitive recovery within broader frameworks, namely, as amelioration of the efficiency of different networks. Furthermore, advances in neuroimaging methodologies, such as the use of whole-brain analysis, tractography, graph analysis, and other sophisticated methodologies of data processing, might be conditioning the interpretation of results and generating new theoretical frameworks. Additionally, structural changes were described in both the grey and white matter, suggesting a neuroprotective effect of cognitive remediation. Cognitive

Over the course of the past decade, contradictory claims have been made regarding the neural bases of deductive reasoning. Researchers have been puzzled by apparent inconsistencies in the literature. Some have even questioned the effectiveness of the methodology used to study the neural bases of deductive reasoning. However, the idea that neuroimaging findings are inconsistent is not based on any quantitative evidence. Here, we report the results of a quantitative meta-analysis of 28 neuroimagingstudies of deductive reasoning published between 1997 and 2010, combining 382 participants. Consistent areas of activations across studies were identified using the multilevel kernel density analysis method. We found that results from neuroimagingstudies are more consistent than what has been previously assumed. Overall, studies consistently report activations in specific regions of a left fronto-parietal system, as well as in the left BG. This brain system can be decomposed into three subsystems that are specific to particular types of deductive arguments: relational, categorical, and propositional. These dissociations explain inconstancies in the literature. However, they are incompatible with the notion that deductive reasoning is supported by a single cognitive system relying either on visuospatial or rule-based mechanisms. Our findings provide critical insight into the cognitive organization of deductive reasoning and need to be accounted for by cognitive theories.

Study Objectives: Attention is a cognitive domain that can be severely affected by sleep deprivation. Previous neuroimagingstudies have used different attention paradigms and reported both increased and reduced brain activation after sleep deprivation. However, due to large variability in sleep deprivation protocols, task paradigms, experimental designs, characteristics of subject populations, and imaging techniques, there is no consensus regarding the effects of sleep loss on the attending brain. The aim of this meta-analysis was to identify brain activations that are commonly altered by acute total sleep deprivation across different attention tasks. Design: Coordinate-based meta-analysis of neuroimagingstudies of performance on attention tasks during experimental sleep deprivation. Methods: The current version of the activation likelihood estimation (ALE) approach was used for meta-analysis. The authors searched published articles and identified 11 sleep deprivation neuroimagingstudies using different attention tasks with a total of 185 participants, equaling 81 foci for ALE analysis. Results: The meta-analysis revealed significantly reduced brain activation in multiple regions following sleep deprivation compared to rested wakefulness, including bilateral intraparietal sulcus, bilateral insula, right prefrontal cortex, medial frontal cortex, and right parahippocampal gyrus. Increased activation was found only in bilateral thalamus after sleep deprivation compared to rested wakefulness. Conclusion: Acute total sleep deprivation decreases brain activation in the fronto-parietal attention network (prefrontal cortex and intraparietal sulcus) and in the salience network (insula and medial frontal cortex). Increased thalamic activation after sleep deprivation may reflect a complex interaction between the de-arousing effects of sleep loss and the arousing effects of task performance on thalamic activity. Citation: Ma N, Dinges DF, Basner M, Rao H. How acute total

Multivariate pattern recognition approaches have recently facilitated the search for reliable neuroimaging-based biomarkers in psychiatric disorders such as schizophrenia. By taking into account the multivariate nature of brain functional and structural changes as well as their distributed localization across the whole brain, they overcome drawbacks of traditional univariate approaches. To evaluate the overall reliability of neuroimaging-based biomarkers, we conducted a comprehensive literature search to identify all studies that used multivariate pattern recognition to identify patterns of brain alterations that differentiate patients with schizophrenia from healthy controls. A bivariate random-effects meta-analytic model was implemented to investigate the sensitivity and specificity across studies as well as to assess the robustness to potentially confounding variables. In the total sample of n=38 studies (1602 patients and 1637 healthy controls), patients were differentiated from controls with a sensitivity of 80.3% (95% CI: 76.7-83.5%) and a specificity of 80.3% (95% CI: 76.9-83.3%). Analysis of neuroimaging modality indicated higher sensitivity (84.46%, 95% CI: 79.9-88.2%) and similar specificity (76.9%, 95% CI: 71.3-81.6%) of rsfMRI studies as compared with structural MRI studies (sensitivity: 76.4%, 95% CI: 71.9-80.4%, specificity of 79.0%, 95% CI: 74.6-82.8%). Moderator analysis identified significant effects of age (p=0.029), imaging modality (p=0.019), and disease stage (p=0.025) on sensitivity as well as of positive-to-negative symptom ratio (p=0.022) and antipsychotic medication (p=0.016) on specificity. Our results underline the utility of multivariate pattern recognition approaches for the identification of reliable neuroimaging-based biomarkers. Despite the clinical heterogeneity of the schizophrenia phenotype, brain functional and structural alterations differentiate schizophrenic patients from healthy controls with 80% sensitivity and specificity.

Objective: This article reviews methods used to teach psychopharmacology to psychiatry residents that utilize principles of adult learning, enlist active participation of residents, and provide faculty with skills to seek, analyze, and use new information over the course of their careers. Methods: The pros and cons of five "nonlecture" methods of…

Positron emission tomography (PET) using radiotracers with high molecular specificity is an important scientific tool in studies of monoamine oxidase (MAO), an important enzyme in the regulation of the neurotransmitters dopamine, norepinephrine, and serotonin as well as the dietary amine, tyramine. MAO occurs in two different subtypes, MAO A and MAO B, which have different substrate and inhibitor specificity and which are different gene products. The highly variable subtype distribution with different species makes human studies of special value. MAO A and B can be imaged in the human brain and certain peripheral organs using PET and carbon-11 (half-life 20.4 minutes) labeled mechanism-based irreversible inhibitors, clorgyline and L -deprenyl, respectively. In this article we introduce MAO and describe the development of these radiotracers and their translation from preclinical studies to the investigation of variables affecting MAO in the human brain and peripheral organs.

In the course of development, the brain undergoes a remarkable process of restructuring as it adapts to the environment and becomes more efficient in processing information. A variety of brain imaging methods can be used to probe how anatomy, connectivity, and function change in the developing brain. Here we review recent discoveries regarding these brain changes in both typically developing individuals and individuals with neurodevelopmental disorders. We begin with typical development, summarizing research on changes in regional brain volume and tissue density, cortical thickness, white matter integrity, and functional connectivity. Space limits preclude the coverage of all neurodevelopmental disorders; instead, we cover a representative selection of studies examining neural correlates of autism, attention deficit/hyperactivity disorder, Fragile X, 22q11.2 deletion syndrome, Williams syndrome, Down syndrome, and Turner syndrome. Where possible, we focus on studies that identify an age by diagnosis interaction, suggesting an altered developmental trajectory. The studies we review generally cover the developmental period from infancy to early adulthood. Great progress has been made over the last 20 years in mapping how the brain matures with MR technology. With ever-improving technology, we expect this progress to accelerate, offering a deeper understanding of brain development, and more effective interventions for neurodevelopmental disorders.

Olfactory deficits on measures of identification, familiarity, and memory are consistently noted in patients with psychotic disorders relative to age-matched controls. Olfactory intensity ratings, however, appear to remain intact while the data on hedonics and detection threshold are inconsistent. Despite the behavioral abnormalities noted, no specific regional brain hypoactivity has been identified in psychosis patients, for any of the olfactory domains. However, an intriguing finding emerged from this review in that the amygdala and pirifom cortices were not noted to be abnormal in hedonic processing (nor was the amygdala identified abnormal in any study) in psychotic disorders. This finding is in contrast to the literature in healthy individuals, in that this brain region is strongly implicated in olfactory processing (particularly for unpleasant odorants). Secondary olfactory cortex (orbitofrontal cortices, thalamus, and insula) was abnormally activated in the studies examined, particularly for hedonic processing. Further research, using consistent methodology, is required for better understanding the neurobiology of olfactory deficits. The authors suggest taking age and sex differences into consideration and further contrasting olfactory subgroups (impaired vs intact) to better our understanding of the heterogeneity of psychotic disorders. PMID:26110122

Structural equation modeling aims at quantifying the strength of causal relationships within a set of interacting variables. Although the literature emphasizes that large sample sizes are required, this method is increasingly used with neuroimaging data of a limited number of subjects to study the relationships between cerebral structures. Here, we use a simulation approach to evaluate its ability to provide accurate information under the constraints of neuroimaging. Artificial samples representing the activity of a virtual set of structures were generated under both recursive and non-recursive connectivity models. Structural equation modeling was performed on these samples, and the quality of the analyses was evaluated by directly comparing the estimated path coefficients with the original ones. The validity and the reliability are shown to decrease with sample size, but the estimated models respect the relative strength of path coefficients in a large percentage of cases. The "smoothing method" appears to be the most appropriate to prevent improper solutions. Both the experimental error and the external structures influencing the network have a weak influence. Accordingly, structural equation modeling can be applied to neuroimaging data, but confidence intervals should be presented together with the path coefficient estimation.

Individuals with spatial neglect following brain injury often show biased performance on landmark bisection tasks (judging if a single item is transected at its midpoint) and search tasks (where they seek target(s) from an array of items). Interestingly, it appears that bisection deficits dissociate from other measures of neglect (including search tasks), and neglect patients with bisection deficits typically have more posterior injury than those without these symptoms. While previous studies in healthy adults have examined each of these tasks independently, our aim was to directly contrast brain activity between these two tasks. Our design used displays that were interpreted as landmark bisection stimuli in some blocks of trials and as search arrays on other trials. Therefore, we used a design where low-level perceptual and motor responses were identical across tasks. Both tasks generated significant activity in bilateral midfusiform gyrus, largely right lateralized activity in the posterior parietal cortex, left lateralized activity in the left motor cortex (consistent with right handed response) and generally right lateralized insular activation. Several brain areas showed task-selective activations when the two tasks were directly compared. Specifically, the superior parietal cortex was selectively activated during the landmark task. On the other hand, the search task caused stronger bilateral activation in the anterior insula, along with midfusiform gyrus, medial superior frontal areas, thalamus and right putamen. This work demonstrates that healthy adults show an anatomical dissociation for visual search and bisection behavior similar to that reported in neurological patients, and provides coordinates for future brain stimulation studies. PMID:21586329

Longitudinal fMRI studies of language production are of interest for evaluating recovery from post-stroke aphasia, but numerous methodological issues remain unresolved, particularly regarding strategies for evaluating single subjects at multiple timepoints. To address these issues, we studied overt picture naming in eleven healthy subjects, scanned four times each at one-month intervals. To evaluate the natural variability present across repeated sessions, repeated scans were directly contrasted in a unified statistical framework on a per-voxel basis. The effect of stimulus familiarity was evaluated using explicitly overtrained pictures, novel pictures, and untrained pictures that were repeated across sessions. For untrained pictures, we found that activation declined across multiple sessions, equally for both novel and repeated stimuli. Thus, no repetition priming for individual stimuli at one-month intervals was found, but rather a general effect of task habituation was present. Using a set of overtrained pictures identical in each session, no decline was found, but activation was minimized and produced less consistent patterns across participants, as measured by intra-class correlation coefficients. Subtraction of a baseline task, in which subjects produced a stereotyped utterance to scrambled pictures, resulted in specific activations in the left inferior frontal gyrus and other language areas for untrained items, while overlearned stimuli relative to pseudo pictures activated only the fusiform gyrus and supplementary motor area. These findings indicate that longitudinal fMRI is an effective means of detecting changes in neural activation magnitude over time, as long as the effect of task habituation is taken into account.

Writing epilepsy is a rare reflex syndrome in which seizures are triggered by writing. We describe a 33-year-old, right-handed man, with a history of juvenile absence epilepsy in remission and a family history of epilepsy, in whom myoclonic jerks precipitated exclusively by writing started at the age of 30. Intensive video/EEG monitoring during neuropsychological tests revealed, at about 1 minute after starting to write, a dystonic posture, followed by myoclonic jerks involving the right hand that shortly after became generalized. Concomitantly, the ictal EEG documented generalized hypersynchronous polyspike-wave discharges, maximal over the right parietocentral area. SPECT revealed an ictal hyperperfusion and interictal hypoperfusion over right parietofrontal regions, and fMRI showed extensive and intense left frontal, supplementary motor area activation, induced by writing. This case study provides some evidence supporting the hypothesis that the mechanism underlying writing-triggered seizures may be a generalized seizure process, with a focal cortical trigger zone, presumed to be the left frontal lobe as suggested by clinical and fMRI data. A relevant role played by the right hemisphere (right parietofrontal region) is postulated in the full-blown expression of reflex epileptogenesis, as supported by EEG and SPECT findings.

Introduction: The orthographic depth hypothesis (Katz and Feldman, 1983) posits that different reading routes are engaged depending on the type of grapheme/phoneme correspondence of the language being read. Shallow orthographies with consistent grapheme/phoneme correspondences favor encoding via non-lexical pathways, where each grapheme is sequentially mapped to its corresponding phoneme. In contrast, deep orthographies with inconsistent grapheme/phoneme correspondences favor lexical pathways, where phonemes are retrieved from specialized memory structures. This hypothesis, however, lacks compelling empirical support. The aim of the present study was to investigate the impact of orthographic depth on reading route selection using a within-subject design. Method: We presented the same pseudowords (PWs) to highly proficient bilinguals and manipulated the orthographic depth of PW reading by embedding them among two separated German or French language contexts, implicating respectively, shallow or deep orthography. High density electroencephalography was recorded during the task. Results: The topography of the ERPs to identical PWs differed 300–360 ms post-stimulus onset when the PWs were read in different orthographic depth context, indicating distinct brain networks engaged in reading during this time window. The brain sources underlying these topographic effects were located within left inferior frontal (German > French), parietal (French > German) and cingular areas (German > French). Conclusion: Reading in a shallow context favors non-lexical pathways, reflected in a stronger engagement of frontal phonological areas in the shallow versus the deep orthographic context. In contrast, reading PW in a deep orthographic context recruits less routine non-lexical pathways, reflected in a stronger engagement of visuo-attentional parietal areas in the deep versus shallow orthographic context. These collective results support a modulation of reading route by orthographic

Review of the literature on psychopharmacology and mental retardation from 1990-1999 found most studies had major methodological flaws. Also, most drug administrations were not based in science, were not evaluated appropriately, and generally did not follow best practices for treatment of persons with mental retardation. A table lists the studies…

While there is no cure for autism spectrum disorder, psychopharmacologic agents are often used with behavioral and educational approaches to treat its comorbid symptoms of hyperactivity, irritability, and aggression. Studies suggest that at least 50% of persons with autism spectrum disorder receive psychotropic medications during their life span.…

Diffusion-weighted imaging (DWI) has transformed the radiological assessment of a variety of cerebral pathologies, in particular acute stroke. In neuroimagingstudies, DWI can also be used to evaluate pathology outside the brain parenchyma, although it is sometimes underutilized for this purpose. In this pictorial review, the principles of DWI are outlined, and 13 cases of abnormal diffusion outside the brain parenchyma are illustrated in order to show DWI as a useful sequence for the evaluation of the following recommended review areas: the dural venous sinuses, internal carotid arteries, meninges, ventricles, cavernous sinus and orbits, skull base and lymph nodes.

The experience of pain in disorders of consciousness is still debated. Neuroimagingstudies, using functional Magnetic Resonance Imaging (fMRI), Positron Emission Tomography (PET), multichannel electroencephalography (EEG) and laser-evoked potentials, suggest that the perception of pain increases with the level of consciousness. Brain activation in response to noxious stimuli has been observed in patients with unresponsive wakefulness syndrome (UWS), which is also referred to as a vegetative state (VS), as well as those in a minimally conscious state (MCS). However, all of these techniques suggest that pain-related brain activation patterns of patients in MCS more closely resemble those of healthy subjects. This is further supported by fMRI findings showing a much greater functional connectivity within the structures of the so-called pain matrix in MCS as compared to UWS/VS patients. Nonetheless, when interpreting the results, a distinction is necessary between autonomic responses to potentially harmful stimuli and conscious experience of the unpleasantness of pain. Even more so if we consider that the degree of residual functioning and cortical connectivity necessary for the somatosensory, affective and cognitive-evaluative components of pain processing are not yet clear. Although procedurally challenging, the particular value of the aforementioned techniques in the assessment of pain in disorders of consciousness has been clearly demonstrated. The study of pain-related brain activation and functioning can contribute to a better understanding of the networks underlying pain perception while addressing clinical and ethical questions concerning patient care. Further development of technology and methods should aim to increase the availability of neuroimaging, objective assessment of functional connectivity and analysis at the level of individual cases as well as group comparisons. This will enable neuroimaging to truly become a clinical tool to reliably investigate

Bilingualism is the ability to use two or more languages with equal or near equal fluency. How the brain, often seamlessly, selects, controls, and switches between languages is an enigma. Neuroimagingstudies offer the unique opportunity to probe the mechanisms underlying bilingual brain function. Non-invasive methods, in particular, functional MRI (fMRI) and event-related potentials (ERPs), have allowed examination in healthy control populations. Whole-head magnetoencephalography (MEG), a relatively new addition to the cadre of neuroimaging tools, offers a combination of the high spatial resolution of fMRI with the high temporal resolution of ERPs. Thus far, MEG has been applied to the study of bilingual receptive language, or bilingual language comprehension. MEG has not yet been applied to the study of bilingual language production as such studies have faced more challenges (see Salmelin, 2007 for a review), and these have only recently been addressed. We review the literature on MEG expressive language studies and point out a direction for the application of MEG to the study of bilingual language production. PMID:23124647

Bilingualism is the ability to use two or more languages with equal or near equal fluency. How the brain, often seamlessly, selects, controls, and switches between languages is an enigma. Neuroimagingstudies offer the unique opportunity to probe the mechanisms underlying bilingual brain function. Non-invasive methods, in particular, functional MRI (fMRI) and event-related potentials (ERPs), have allowed examination in healthy control populations. Whole-head magnetoencephalography (MEG), a relatively new addition to the cadre of neuroimaging tools, offers a combination of the high spatial resolution of fMRI with the high temporal resolution of ERPs. Thus far, MEG has been applied to the studies of bilingual receptive language, or bilingual language comprehension. MEG has not yet been applied to the study of bilingual language production as such studies have faced more challenges (see Salmelin, 2007 for a review), and these have only recently been addressed. Here, we review the literature on MEG expressive language studies and point out a direction for the application of MEG to the study of bilingual language production.

The most common neurodevelopmental disorders (e.g., developmental dyslexia (DD), autism, attention-deficit hyperactivity disorder (ADHD)) have been the subject of numerous neuroimagingstudies, leading to certain brain regions being identified as neural correlates of these conditions, referring to a neural signature of disorders. Developmental coordination disorder (DCD), however, remains one of the least understood and studied neurodevelopmental disorders. Given the acknowledged link between motor difficulties and brain features, it is surprising that so few research studies have systematically explored the brains of children with DCD. The aim of the present review was to ascertain whether it is currently possible to identify a neural signature for DCD, based on the 14 magnetic resonance imaging neuroimagingstudies that have been conducted in DCD to date. Our results indicate that several brain areas are unquestionably linked to DCD: cerebellum, basal ganglia, parietal lobe, and parts of the frontal lobe (medial orbitofrontal cortex and dorsolateral prefrontal cortex). However, research has been too sparse and studies have suffered from several limitations that constitute a serious obstacle to address the question of a well-established neural signature for DCD. PMID:28018285

Fragile X syndrome (FraX) remains the most common inherited cause of intellectual disability and provides a valuable model for studying gene-brain-behavior relationships. Over the past 15 years, structural and functional magnetic resonance imaging studies have emerged with the goal of better understanding the neural pathways contributing to the cognitive and behavioral outcomes seen in individuals with FraX. Specifically, structural MRI studies have established and begun to refine the specific topography of neuroanatomical variation associated with FraX. In addition, functional neuroimagingstudies have begun to elucidate the neural underpinnings of many of the unique characteristics of FraX including difficulties with eye gaze, executive functioning, and behavioral inhibition. This review highlights studies with a focus on the relevant gene-brain-behavior connections observed in FraX. The relationship of brain regions and activation patterns to FMRP are discussed as well as the clinical cognitive and behavioral correlates of these neuroimaging findings. PMID:20014368

Humans experience significant physical and mental changes from birth to adulthood, and a variety of perceptual, cognitive and motor functions mature over the course of approximately 20 years following birth. To deeply understand such developmental processes, merely studying behavioral changes is not sufficient; simultaneous investigation of the development of the brain may lead us to a more comprehensive understanding. Recent advances in noninvasive neuroimaging technologies largely contribute to this understanding. Here, it is very important to consider the development of the brain from the perspectives of "structure" and "function" because both structure and function of the human brain mature slowly. In this review, we first discuss the process of structural brain development, i.e., how the structure of the brain, which is crucial when discussing functional brain development, changes with age. Second, we introduce some representative studies and the latest studies related to the functional development of the brain, particularly for visual, facial recognition, and social cognition functions, all of which are important for humans. Finally, we summarize how brain science can contribute to developmental study and discuss the challenges that neuroimaging should address in the future.

Humans experience significant physical and mental changes from birth to adulthood, and a variety of perceptual, cognitive and motor functions mature over the course of approximately 20 years following birth. To deeply understand such developmental processes, merely studying behavioral changes is not sufficient; simultaneous investigation of the development of the brain may lead us to a more comprehensive understanding. Recent advances in noninvasive neuroimaging technologies largely contribute to this understanding. Here, it is very important to consider the development of the brain from the perspectives of “structure” and “function” because both structure and function of the human brain mature slowly. In this review, we first discuss the process of structural brain development, i.e., how the structure of the brain, which is crucial when discussing functional brain development, changes with age. Second, we introduce some representative studies and the latest studies related to the functional development of the brain, particularly for visual, facial recognition, and social cognition functions, all of which are important for humans. Finally, we summarize how brain science can contribute to developmental study and discuss the challenges that neuroimaging should address in the future. PMID:27695409

Functional neuroimaging is one of the most powerful means available for investigating the pathophysiology of psychiatric disorders. In this review, we shall focus on the different ways that it can be employed to this end, describing the major findings in the field in the context of different methodological approaches. We will also discuss practical issues that are particular to studying psychiatric disorders and the potential contribution of functional neuroimaging to future psychiatric research. PMID:10466156

Imaging is pivotal in the evaluation and management of patients with seizure disorders. Elegant structural neuroimaging with magnetic resonance imaging (MRI) may assist in determining the etiology of focal epilepsy and demonstrating the anatomical changes associated with seizure activity. The high diagnostic yield of MRI to identify the common pathological findings in individuals with focal seizures including mesial temporal sclerosis, vascular anomalies, low-grade glial neoplasms and malformations of cortical development has been demonstrated. Positron emission tomography (PET) is the most commonly performed interictal functional neuroimaging technique that may reveal a focal hypometabolic region concordant with seizure onset. Single photon emission computed tomography (SPECT) studies may assist performance of ictal neuroimaging in patients with pharmacoresistant focal epilepsy being considered for neurosurgical treatment. This chapter highlights neuroimaging developments and innovations, and provides a comprehensive overview of the imaging strategies used to improve the care and management of people with epilepsy. PMID:27430454

Imbalances of neurotransmitter systems, particularly serotonin (5-HT) and dopamine (DA), are known to play an essential role in many neuropsychiatric disorders. The transient manipulation of such systems through the alteration of their amino acid precursors is a well-known research tool. Among these methods are alterations of tryptophan, the essential amino acid (AA) precursor of 5-HT, as well as manipulations of tyrosine and phenylalanine, the AA precursors of DA, which can be metabolized into norepinephrine and subsequently into epinephrine. These systems can be loaded by applying a large dose of these AAs or depleted by applying an amino acid mixture lacking the respective AAs serving as precursors. Functional neuroimaging has given insights into differential brain activation patterns and functions depending on the tasks performed, pharmacological treatments or specific disorders. Such research has shed light on the function of many brain areas as well as their interactions. The combination of AA challenge approaches with neuroimaging techniques has been subject of numerous studies. Overall, the studies conducted in this particular field of research have shown that AA challenge techniques are valid and effective research tools that allow the investigation of serotonergic and dopaminergic systems without causing serious side effects or long-term damage to the subjects. In this review, we will present an overview of the results obtained so far and discuss the implications of these findings as well as open questions that remain to be answered.

Functional, molecular and genetic neuroimaging has highlighted the existence of brain anomalies and neural vulnerability factors related to obesity and eating disorders such as binge eating or anorexia nervosa. In particular, decreased basal metabolism in the prefrontal cortex and striatum as well as dopaminergic alterations have been described in obese subjects, in parallel with increased activation of reward brain areas in response to palatable food cues. Elevated reward region responsivity may trigger food craving and predict future weight gain. This opens the way to prevention studies using functional and molecular neuroimaging to perform early diagnostics and to phenotype subjects at risk by exploring different neurobehavioral dimensions of the food choices and motivation processes. In the first part of this review, advantages and limitations of neuroimaging techniques, such as functional magnetic resonance imaging (fMRI), positron emission tomography (PET), single photon emission computed tomography (SPECT), pharmacogenetic fMRI and functional near-infrared spectroscopy (fNIRS) will be discussed in the context of recent work dealing with eating behavior, with a particular focus on obesity. In the second part of the review, non-invasive strategies to modulate food-related brain processes and functions will be presented. At the leading edge of non-invasive brain-based technologies is real-time fMRI (rtfMRI) neurofeedback, which is a powerful tool to better understand the complexity of human brain–behavior relationships. rtfMRI, alone or when combined with other techniques and tools such as EEG and cognitive therapy, could be used to alter neural plasticity and learned behavior to optimize and/or restore healthy cognition and eating behavior. Other promising non-invasive neuromodulation approaches being explored are repetitive transcranial magnetic stimulation (rTMS) and transcranial direct-current stimulation (tDCS). Converging evidence points at the value of

Functional, molecular and genetic neuroimaging has highlighted the existence of brain anomalies and neural vulnerability factors related to obesity and eating disorders such as binge eating or anorexia nervosa. In particular, decreased basal metabolism in the prefrontal cortex and striatum as well as dopaminergic alterations have been described in obese subjects, in parallel with increased activation of reward brain areas in response to palatable food cues. Elevated reward region responsivity may trigger food craving and predict future weight gain. This opens the way to prevention studies using functional and molecular neuroimaging to perform early diagnostics and to phenotype subjects at risk by exploring different neurobehavioral dimensions of the food choices and motivation processes. In the first part of this review, advantages and limitations of neuroimaging techniques, such as functional magnetic resonance imaging (fMRI), positron emission tomography (PET), single photon emission computed tomography (SPECT), pharmacogenetic fMRI and functional near-infrared spectroscopy (fNIRS) will be discussed in the context of recent work dealing with eating behavior, with a particular focus on obesity. In the second part of the review, non-invasive strategies to modulate food-related brain processes and functions will be presented. At the leading edge of non-invasive brain-based technologies is real-time fMRI (rtfMRI) neurofeedback, which is a powerful tool to better understand the complexity of human brain-behavior relationships. rtfMRI, alone or when combined with other techniques and tools such as EEG and cognitive therapy, could be used to alter neural plasticity and learned behavior to optimize and/or restore healthy cognition and eating behavior. Other promising non-invasive neuromodulation approaches being explored are repetitive transcranial magnetic stimulation (rTMS) and transcranial direct-current stimulation (tDCS). Converging evidence points at the value of

Practical clinical trials (PCT) are randomized experiments under typical practice conditions with the aim of testing the “real life” benefits and risks of therapeutic interventions. Influential PCTs have been conducted in cardiology, oncology, and internal medicine. Psychotropic medications are widely and increasingly used in medical practice. This review examines recent progress in conducting PCTs in psychopharmacology. The January 2000 – October 2014 MEDLINE, Scopus, and ClinicalTrials.gov databases were searched for peer-reviewed publications of PCTs with at least 100 subjects per treatment arm. Most PCTs in psychiatry evaluated mental health services or psychosocial interventions rather than specific pharmacotherapies. Of 157 PCTs in psychiatry, 30 (19%) were in psychopharmacology, with a median of 2 publications per year and no increase over the period of observation. Sample size ranged from 200 to 18,154; only 11 studies randomized 500 patients or more. Psychopharmacology PCTs were equally likely to be funded by industry as by public agencies. There were 10 PCTs of antidepressants, for a total of 4,206 patients (in comparison with at least 46 PCT of antihypertensive medications, for a total of 208,014 patients). Some psychopharmacology PCTs used suicidal behavior, treatment discontinuation, or mortality as primary outcome, and produced effectiveness and safety data that have influenced both practice guidelines and regulatory decisions. PCTs can constitute an important source of information for clinicians, patients, regulators, and policy makers, but have been relatively underutilized in psychopharmacology. Electronic medical records and integrated practice research networks offer promising platforms for a more efficient conduct of PCTs. PMID:25679131

Practical clinical trials (PCTs) are randomized experiments under typical practice conditions with the aim of testing the "real-life" benefits and risks of therapeutic interventions. Influential PCTs have been conducted in cardiology, oncology, and internal medicine. Psychotropic medications are widely and increasingly used in medical practice. This review examines recent progress in conducting PCTs in psychopharmacology. The January 2000 to October 2014 MEDLINE, Scopus, and ClinicalTrials.gov databases were searched for peer-reviewed publications of PCTs with at least 100 subjects per treatment arm. Most PCTs in psychiatry evaluated mental health services or psychosocial interventions rather than specific pharmacotherapies. Of 157 PCTs in psychiatry, 30 (19%) were in psychopharmacology, with a median of 2 publications per year and no increase during the period of observation. Sample size ranged from 200 to 18,154; only 11 studies randomized 500 patients or more. Psychopharmacology PCTs were equally likely to be funded by industry as by public agencies. There were 10 PCTs of antidepressants, for a total of 4206 patients (in comparison with at least 46 PCTs of antihypertensive medications, for a total of 208,014 patients). Some psychopharmacology PCTs used suicidal behavior, treatment discontinuation, or mortality as primary outcome and produced effectiveness and safety data that have influenced both practice guidelines and regulatory decisions. Practical clinical trials can constitute an important source of information for clinicians, patients, regulators, and policy makers but have been relatively underused in psychopharmacology. Electronic medical records and integrated practice research networks offer promising platforms for a more efficient conduct of PCTs.

At present, no evidence-based effective pharmacologic options are available for treating the core deficits of autism spectrum disorders (ASDs), which are best addressed by behavioral and educational interventions. However, such evidence exists for several of the frequently associated/comorbid symptoms such as aggression and severe irritability, hyperactivity, and repetitive behaviors, which can become a major source of additional distress and interference in functioning. This article offers information on the psychopharmacology of ASD that is current, relevant, and organized in a user-friendly manner, to form a concise but informative reference guide for primary pediatric clinicians.

The advent of functional neuroimaging techniques has allowed to address the question of the role of the brain in a new light, being now able to record brain activity under different kinds of perceptual, cognitive or motor paradigms. Two exponentially emerging fields, i.e. social and affective neurosciences, converge on topics such as brain processing of emotional information issued by the congeners. As any social interaction obbeys a motivational dimension of interattraction, it is therefore important to study the role of the brain in specific functional contexts. In this paper we show how the emergence of a new field crystallized around the study of brain circuits involved in sexual affiliation has helped providing important results to understand the brain’s role in social motivated interactions. Specifically, these studies show for this involvement a central physiological component and its cortical representation that seems to be essential for social interactions with motivational component. PMID:21966343

The attachment and the caregiving system are complementary systems which are active simultaneously in infant and mother interactions. This ensures the infant survival and optimal social, emotional, and cognitive development. In this brief review we first define the characteristics of these two behavioral systems and the theory that links them, according to what Bowlby called the “attachment-caregiving social bond” (Bowlby, 1969). We then follow with those neuroimagingstudies that have focused on this particular issue, i.e., those which have studied the activation of the careging system in women (using infant stimuli) and have explored how the individual attachment model (through the Adult Attachment Interview) modulates its activity. Studies report altered activation in limbic and prefrontal areas and in basal ganglia and hypothalamus/pituitary regions. These altered activations are thought to be the neural substrate of the attachment-caregiving systems interaction. PMID:26379578

Lippia multiflora (L.m.) is a verbenacea used in Congo as conventional tea decoction. No traditional indication is known in this country. Nevertheless, in Ghana the plant is used for the treatment of arterial hypertension. The aim of this study is to investigate the psychotropic activity of the aqueous extract of L.m. using the classical tests of experimental psychopharmacology. The extract of L.m. is constituted by lyophilisated powder obtained from an infusion of dried leaves. Different doses are prepared: 200, 400, 600, 800, 1,000 and 1,200 mg/kg dissolved in 1 ml of NaCl 0.9%. L.m. is administered by intraperitoneal or oral route. The wistar rats of both sexes, weighing between 150-200 g, are used. Animal's behaviour is observed macroscopically. The spontaneous motor activity is appreciated by using the number of squares crossed by animal with the four paws in ten minutes (Martin and al. method slightly modified). The rectal temperature is measured. The effect of L.m. on stereotypies induced by apomorphin and anesthesia induced by phenobarbital are studied. The traction test is used to investigate the muscle relaxant effect of L.m. and analgesic activity is evaluated by using acetic acid and hot plate methods by comparison with diazepam 2 and 4 mg/kg. Fischer-t test is used for the statistical analysis of results. L.m. is well tolerated by rats. No mortality is observed with the doses used. So the doses of 200, 400 and 600 mg/kg were selected for experiments. At theses doses L.m. caused: a precocious ataxia, a sedation, a ptosis and a yellow coloration of urines, these effects are dose dependent; a significant reduction of spontaneous motor activity: control 61.60 +/- 6.48, L.m. 200: 16.40 +/- 5.68 (P < 0.01), L.m. 400: 12.20 +/- 2.01 and L.m. 600: 9.60 +/- 1.90 (P < 0.01); no modification of rectal temperature and apomorphin stereotypies; a reduction of sleep latence: control 22.40 +/- 1.89 min, L.m. 200: 17.20 +/- 2.74 min (P < 0.01), L.m. 400: 13.80 +/- 1

Emotion theory emphasizes the distinction between social vs non-social emotional-processing (E-P) although few functional neuroimagingstudies have examined whether the neural systems that mediate social vs non-social E-P are similar or distinct. The present fMRI study of script-driven imagery in 20 women demonstrates that social E-P, independent of valence, more strongly recruits brain regions involved in social- and self-referential processing, specifically the dorsomedial prefrontal cortex, posterior cingulate/precuneus, bilateral temporal poles, bilateral temporoparietal junction and right amygdala. Functional response within brain regions involved in E-P was also significantly more pronounced during negatively relative to positively valenced E-P. Finally, the effect for social E-P was increased for positive relative to negative stimuli in many of these same regions. Future research directions for social and affective neuroscience are discussed. PMID:20525743

Neuroscience research on the social evaluation of faces has accumulated over the last decade, yielding divergent results. We used a meta-analytic technique, multi-level kernel density analysis (MKDA), to analyze 29 neuroimagingstudies on face evaluation. Across negative face evaluations, we observed the most consistent activations in bilateral amygdala. Across positive face evaluations, we observed the most consistent activations in medial prefrontal cortex, pregenual anterior cingulate cortex (pgACC), medial orbitofrontal cortex (mOFC), left caudate and nucleus accumbens (NAcc). Based on additional analyses comparing linear and non-linear responses, we propose a ventral/dorsal dissociation within the amygdala, wherein separate populations of neurons code for face valence and intensity, respectively. Finally, we argue that some of the differences between studies are attributable to differences in the typicality of face stimuli. Specifically, extremely attractive faces are more likely to elicit responses in NAcc/caudate and mOFC. PMID:22287188

In the past decade, research has accumulated suggesting that excessive Internet use can lead to the development of a behavioral addiction. Internet addiction has been considered as a serious threat to mental health and the excessive use of the Internet has been linked to a variety of negative psychosocial consequences. The aim of this review is to identify all empirical studies to date that used neuroimaging techniques to shed light upon the emerging mental health problem of Internet and gaming addiction from a neuroscientific perspective. Neuroimagingstudies offer an advantage over traditional survey and behavioral research because with this method, it is possible to distinguish particular brain areas that are involved in the development and maintenance of addiction. A systematic literature search was conducted, identifying 18 studies. These studies provide compelling evidence for the similarities between different types of addictions, notably substance-related addictions and Internet and gaming addiction, on a variety of levels. On the molecular level, Internet addiction is characterized by an overall reward deficiency that entails decreased dopaminergic activity. On the level of neural circuitry, Internet and gaming addiction led to neuroadaptation and structural changes that occur as a consequence of prolonged increased activity in brain areas associated with addiction. On a behavioral level, Internet and gaming addicts appear to be constricted with regards to their cognitive functioning in various domains. The paper shows that understanding the neuronal correlates associated with the development of Internet and gaming addiction will promote future research and will pave the way for the development of addiction treatment approaches.

Heritability estimation has become an important tool for imaging genetics studies. The large number of voxel- and vertex-wise measurements in imaging genetics studies presents a challenge both in terms of computational intensity and the need to account for elevated false positive risk because of the multiple testing problem. There is a gap in existing tools, as standard neuroimaging software cannot estimate heritability, and yet standard quantitative genetics tools cannot provide essential neuroimaging inferences, like family-wise error corrected voxel-wise or cluster-wiseP-values. Moreover, available heritability tools rely on P-values that can be inaccurate with usual parametric inference methods. In this work we develop fast estimation and inference procedures for voxel-wise heritability, drawing on recent methodological results that simplify heritability likelihood computations (Blangero etal., 2013). We review the family of score and Wald tests and propose novel inference methods based on explained sum of squares of an auxiliary linear model. To address problems with inaccuracies with the standard results used to find P-values, we propose four different permutation schemes to allow semi-parametric inference (parametric likelihood-based estimation, non-parametric sampling distribution). In total, we evaluate 5 different significance tests for heritability, with either asymptotic parametric or permutation-basedP-value computations. We identify a number of tests that are both computationally efficient and powerful, making them ideal candidates for heritability studies in the massive data setting. We illustrate our method on fractional anisotropy measures in 859 subjects from the Genetics of Brain Structure study. PMID:25812717

In neuroscience, collaboration and data sharing are undermined by concerns over the management of protected health information (PHI) and personal identifying information (PII) in neuroimage datasets. The HIPAA Privacy Rule mandates measures for the preservation of subject privacy in neuroimagingstudies. Unfortunately for the researcher, the management of information privacy is a burdensome task. Wide scale data sharing of neuroimages is challenging for three primary reasons: (i) A dearth of tools to systematically expunge PHI/PII from neuroimage data sets, (ii) a facility for tracking patient identities in redacted datasets has not been produced, and (iii) a sanitization workflow remains conspicuously absent. This article describes the XNAT Redaction Toolkit—an integrated redaction workflow which extends a popular neuroimage data management toolkit to remove PHI/PII from neuroimages. Quickshear defacing is also presented as a complementary technique for deidentifying the image data itself. Together, these tools improve subject privacy through systematic removal of PII/PHI. PMID:24179597

Darwin's seminal publications in the nineteenth century laid the foundation for an evolutionary approach to psychology and psychiatry. Advances in 20th century evolutionary theory facilitated the development of evolutionary psychology and psychiatry as recognized areas of scientific investigation. In this century, advances in understanding the molecular basis of evolution, of the mind, and of psychopathology, offer the possibility of an integrated approach to understanding the proximal (psychobiological) and distal (evolutionary) mechanisms of interest to psychiatry and psychopharmacology. There is, for example, growing interest in the question of whether specific genetic variants mediate psychobiological processes that have evolutionary value in specific contexts, and of the implications of this for understanding the vulnerability to psychopathology and for considering the advantages and limitations of pharmacotherapy. The evolutionary value, and gene-environmental mediation, of early life programming is potentially a particularly rich area of investigation. Although evolutionary approaches to psychology and to medicine face important conceptual and methodological challenges, current work is increasingly sophisticated, and may prove to be an important foundational discipline for clinicians and researchers in psychiatry and psychopharmacology.

Despite the recent DSM-5 review of somatoform disorders, which are now called somatic symptom and related disorders, the categorical definitions of these syndromes have inherent limitations because their causal mechanism or presumed aetiologies are still unknown. These limitations may affect everyday clinical practice and decision-making abilities. As a result, physicians have limited information at their disposal to treat these patients. Furthermore, the clinical presentations of somatic disorders may vary a lot. The purpose of this chapter is to illustrate a psychopathological dimensional approach to the somatising patient. This approach is constantly unconsciously applied in clinical practice using continuous variables, such as rating scales. Moreover, treatment strategies might be improved by adding a dimensional approach, simply recognising the prominent components of the presenting psychopathology of a given patient and addressing them with drugs according to their different mechanisms, targeting circuits and neurotransmitters. Some authors have proposed a shift from the nosological to functional application of psychotropic drugs, in which functional psychopharmacology will be dysfunction oriented and therefore inevitably geared towards utilising drug combinations. Here, we present a summary of the advantages of functional/dimensional psychopharmacology for the treatment of somatic symptoms and related disorders.

Previous neuropsychological studies on acquired dyslexia revealed a double dissociation in reading impairments. Patients with phonological dyslexia have selective difficulty in reading pseudo-words, while those with surface dyslexia misread exception words. This double dissociation in reading abilities has often been reported in brain-damaged patients, but it has not been consistently shown in patients with neurodegenerative diseases. In this study, we investigated reading impairments and their anatomical correlates in various neurodegenerative diseases. First, we performed a behavioral analysis to characterize the reading of different word types in primary progressive aphasia (PPA). Then, we conducted a voxel-based morphometry neuroimagingstudy to map the brain areas in which gray matter volume correlated with the accurate reading of exception and pseudo-words. The results showed a differential pattern of exception and pseudo-word reading abilities in different clinical variants of PPA. Patients with semantic dementia, a disorder characterized by selective loss of semantic memory, revealed a pattern of surface dyslexia, while patients with logopenic/phonological progressive aphasia, defined by phonological loop deficits, showed phonological dyslexia. Neuroimaging results showed that exception word reading accuracy correlated with gray matter volume in the left anterior temporal structures, including the temporal pole, the anterior superior and middle temporal and fusiform gyri, while pseudo-word reading accuracy correlated with left temporoparietal regions, including the posterior superior and middle temporal and fusiform gyri, and the inferior parietal lobule. These results suggest that exception and pseudo-word reading not only rely upon different language mechanisms selectively damaged in PPA, but also that these processes are sustained by separate brain structures.

Prosody refers to the melodic and rhythmic aspects of speech. Two forms of prosody are typically distinguished: 'affective prosody' refers to the expression of emotion in speech, whereas 'linguistic prosody' relates to the intonation of sentences, including the specification of focus within sentences and stress within polysyllabic words. While these two processes are united by their use of vocal pitch modulation, they are functionally distinct. In order to examine the localization and lateralization of speech prosody in the brain, we performed two voxel-based meta-analyses of neuroimagingstudies of the perception of affective and linguistic prosody. There was substantial sharing of brain activations between analyses, particularly in right-hemisphere auditory areas. However, a major point of divergence was observed in the inferior frontal gyrus: affective prosody was more likely to activate Brodmann area 47, while linguistic prosody was more likely to activate the ventral part of area 44.

Psychotropic medications prescribed frequently to children and adolescents for the treatment of anxiety, depression, and attention deficit hyperactivity disorder are reviewed. Pediatric pharmacological options based on double-blind, randomized studies are examined. We advocate that psychotropic medications be used only in conjunction with…

Neuroimaging findings which identify normal brain development trajectories are presented. Results show that early brain development begins with the neural tube formation and ends with myelintation. How disturbances in brain development patterns are related to childhood psychiatric disorders is examined.

OBJECTIVE: To develop pharmacotherapies for the orphan disease lycanthropy through the pursuit of the etiologic hypothesis of a genetically determined hypersecretion of endogenous lycanthropogens. DESIGN: Quadruple-blind, Rubik's Cube matrix analysis. SETTING: Community practice and malpractice. PARTICIPANTS: Subjects selected from inbred Ruficolla populations in Mississippi, Georgia, North Carolina and Minnesota. All who entered the study finished it. INTERVENTIONS: Chemical screening of blood samples over a hypothesized secretory cycle of lycanthropogen peaking on the day of maximum lunar illumination. Administration of synthetic lycanthropogens for behavioural testing. Experimental lycosomatization through the illumination method of Kirschbaum. OUTCOME MEASURES: None were post hoc, but some are still in hock. MAIN RESULTS: Two putative lycanthropogens were isolated from the blood samples. Structural elucidation and synthesis permitted animal and clinical trials; in each of these, behavioural dysfunction was observed. Antilycanthropogen strategies included application of the principle of caged compounds and generation of a therapeutic immunoglobulin. The effects of a newly developed antihirsutic agent seemed promising. An interaction of the lycanthropogen-secretion system and ethanol was noted, which may explain behavioural aspects of alcoholism. CONCLUSIONS: The incidence of lycomania in North America is underestimated. Soon-to-be-available pharmacotherapies should promote its early detection and treatment. Full control may depend upon advances in gene therapy. PMID:1555146

No standard treatment exists for the DSM-IV Impulse Control Disorders, Not Elsewhere Classified, including Compulsive Buying Disorder. This paper reviews the suggested pharmacotherapies for this disorder and their theoretical basis. McElroy et al. first reported benefit from antidepressant therapy in three cases of Compulsive Buying Disorder with comorbid depression and anxiety. In a retrospective chart review, McElroy's group reported on 20 patients that benefited from antidepressants, often in combination with mood stabilizers. Lejoyeux reported on two patients in whom treatment of a comorbid mood disorder led to remission of compulsive buying behavior. Black reported fluvoxamine to be effective in patients without comorbid major depression, suggesting that improvement was independent of the treatment of mood symptoms. Kim reported improvement with naltrexone, an opioid antagonist, in a case series. Two double-blind placebo-controlled trials found fluvoxamine no better than placebo; however, in both studies patients kept shopping logs, which may have confounded the results. An open-label trial of citalopram and a double-blind crossover trial which excluded shopping logs both reported positive results. Twelve-month follow-up data for the open-label group found that remission rates at quarterly time points were independent of continuing drug therapy. The data reviewed above suggest that pharmacologic interventions may be effective for compulsive buying disorder. Whether pharmacological treatment is superior to placebo and whether it is more, less or equally effective compared to psychotherapeutic interventions remains to be established.

Motivation Multivariate quantitative traits arise naturally in recent neuroimaging genetics studies, in which both structural and functional variability of the human brain is measured non-invasively through techniques such as magnetic resonance imaging (MRI). There is growing interest in detecting genetic variants associated with such multivariate traits, especially in genome-wide studies. Random forests (RFs) classifiers, which are ensembles of decision trees, are amongst the best performing machine learning algorithms and have been successfully employed for the prioritisation of genetic variants in case-control studies. RFs can also be applied to produce gene rankings in association studies with multivariate quantitative traits, and to estimate genetic similarities measures that are predictive of the trait. However, in studies involving hundreds of thousands of SNPs and high-dimensional traits, a very large ensemble of trees must be inferred from the data in order to obtain reliable rankings, which makes the application of these algorithms computationally prohibitive. Results We have developed a parallel version of the RF algorithm for regression and genetic similarity learning tasks in large-scale population genetic association studies involving multivariate traits, called PaRFR (Parallel Random Forest Regression). Our implementation takes advantage of the MapReduce programming model and is deployed on Hadoop, an open-source software framework that supports data-intensive distributed applications. Notable speed-ups are obtained by introducing a distance-based criterion for node splitting in the tree estimation process. PaRFR has been applied to a genome-wide association study on Alzheimer's disease (AD) in which the quantitative trait consists of a high-dimensional neuroimaging phenotype describing longitudinal changes in the human brain structure. PaRFR provides a ranking of SNPs associated to this trait, and produces pair-wise measures of genetic proximity

This review surveys human event-related brain potential (ERP) and event-related magnetic field (ERF) approaches to psychopharmacology and psychopathology, and the way in which they complement behavioral studies and other neuroimaging modalities. The major paradigms involving ERP/ERF are P50 suppression, loudness-dependent auditory evoked potential (LDAEP), mismatch negativity (MMN), P300, mental chronometry, inhibitory control, and conflict processing (eg, error-related negativity (ERN)). Together these paradigms cover a range of more bottom-up driven to more top-down controlled processes. A number of relationships between the major neurotransmitter systems and electrocortical mechanisms are highlighted. These include the role of dopamine in conflict processing, and perceptual processing vs motor preparation; the role of serotonin in P50 suppression, LDAEP, and MMN; glutamate/NMDA and MMN; and the role of acetylcholine in P300 generation and memory-related processes. A preliminary taxonomy for these relationships is provided, which should be helpful in attuning possible new treatments or new applications of existing treatments to various disorders. PMID:20927044

This review surveys human event-related brain potential (ERP) and event-related magnetic field (ERF) approaches to psychopharmacology and psychopathology, and the way in which they complement behavioral studies and other neuroimaging modalities. The major paradigms involving ERP/ERF are P50 suppression, loudness-dependent auditory evoked potential (LDAEP), mismatch negativity (MMN), P300, mental chronometry, inhibitory control, and conflict processing (eg, error-related negativity (ERN)). Together these paradigms cover a range of more bottom-up driven to more top-down controlled processes. A number of relationships between the major neurotransmitter systems and electrocortical mechanisms are highlighted. These include the role of dopamine in conflict processing, and perceptual processing vs motor preparation; the role of serotonin in P50 suppression, LDAEP, and MMN; glutamate/NMDA and MMN; and the role of acetylcholine in P300 generation and memory-related processes. A preliminary taxonomy for these relationships is provided, which should be helpful in attuning possible new treatments or new applications of existing treatments to various disorders.

Most of our current understanding of the neurobiology, neuroanatomy and psychopharmacology of sexual behavior and ejaculatory function has been derived from preclinical studies in the rat. When a large population of male rats is tested on sexual activity during a number of successive tests, over time individual rats display a very stable sexual behavior that is either slow, normal or fast as characterized by the number of ejaculations performed. These sexual endophenotypes are postulated as rat counterparts of premature (fast rats) or retarded ejaculation (slow rats). Psychopharmacology in these endophenotypes helps to delineate the underlying mechanisms and pathology. This is illustrated by the effects of serotonergic antidepressants and serotonergic compounds on sexual and ejaculatory behavior of rats. These preclinical studies and models contribute to a better understanding of the neurobiology of ejaculation and boost the development of novel drug targets to treat ejaculatory disorders such as premature and retarded ejaculation.

The neural mechanisms responsible for spontaneous yawning as well as contagious yawning are not well characterized. Neuroimaging is an essential tool for helping to identify the seminal neural structures and their inter-related functions to carry out this complex stereotyped motor program. Studies to date have explored the structural neural correlates of yawning through a series of lesion-based case reports and identified participatory structures at various levels of the central nervous system. Functional neuroimaging methods like fMRI have also shed led on the genesis of contagious yawning, though cohesive models explaining the neural mechanisms of contagious motor programs such as yawning remain limited.

Brain imaging research allows direct assessment of structural and functional brain abnormalities, and thereby provides an improved methodology for studying neurobiological factors predisposing to violent and aggressive behavior. This paper reviews 20 brain imaging studies using four different types of neuroimaging techniques that were conducted in…

In a quantitative meta-analysis, using the activation likelihood estimation method, we examined the neural regions involved in bilingual cognitive control, particularly when engaging in switching between languages. The purpose of this study was to evaluate the bilingual cognitive control model based on a qualitative analysis [Abutalebi, J., & Green, D. W. (2008). Control mechanisms in bilingual language production: Neural evidence from language switching studies. Language and Cognitive Processes, 23, 557–582.]. After reviewing 128 peer-reviewed articles, ten neuroimagingstudies met our inclusion criteria and in each study, bilinguals switched between languages in response to cues. We isolated regions involved in voluntary language switching, by including reported contrasts between the switching conditions and high level baseline conditions involving similar tasks but requiring the use of only one language. Eight brain regions showed significant and reliable activation: left inferior frontal gyrus, left middle temporal gyrus, left middle frontal gyrus, right precentral gyrus, right superior temporal gyrus, midline pre-SMA and bilateral caudate nuclei. This quantitative result is consistent with bilingual aphasia studies that report switching deficits associated with lesions to the caudate nuclei or prefrontal cortex. It also extends the previously reported qualitative model. We discuss the implications of the findings for accounts of bilingual cognitive control. PMID:24795491

Prenatal methamphetamine exposure (PME) is a significant problem in several parts of the world and poses important health risks for the developing fetus. Research on the short- and long-term outcomes of PME is scarce, however. Here, we summarize present knowledge on the cognitive and behavioral outcomes of PME, based on a review of the neuroimaging, neuropsychology, and neuroscience literature published in the past 15 years. Several studies have reported that the behavioral and cognitive sequelae of PME include broad deficits in the domains of attention, memory, and visual-motor integration. Knowledge regarding brain-behavior relationships is poor, however, in large part because imaging studies are rare. Hence, the effects of PME on developing neurocircuitry and brain architecture remain speculative, and are largely deductive. Some studies have implicated the dopamine-rich fronto-striatal pathways; however, cognitive deficits (e.g., impaired visual-motor integration) that should be associated with damage to those pathways are not manifested consistently across studies. We conclude by discussing challenges endemic to research on prenatal drug exposure, and argue that they may account for some of the inconsistencies in the extant research on PME. Studies confirming predicted brain-behavior relationships in PME, and exploring possible mechanisms underlying those relationships, are needed if neuroscience is to address the urgency of this growing public health problem.

Stuttering is a speech disorder characterised by repetitions, prolongations and blocks that disrupt the forward movement of speech. An earlier meta-analysis of brain imaging studies of stuttering (Brown et al., 2005) revealed a general trend towards rightward lateralization of brain activations and hyperactivity in the larynx motor cortex bilaterally. The present study sought not only to update that meta-analysis with recent work but to introduce an important distinction not present in the first study, namely the difference between 'trait' and 'state' stuttering. The analysis of trait stuttering compares people who stutter (PWS) with people who do not stutter when behaviour is controlled for, i.e., when speech is fluent in both groups. In contrast, the analysis of state stuttering examines PWS during episodes of stuttered speech compared with episodes of fluent speech. Seventeen studies were analysed using activation likelihood estimation. Trait stuttering was characterised by the well-known rightward shift in lateralization for language and speech areas. State stuttering revealed a more diverse pattern. Abnormal activation of larynx and lip motor cortex was common to the two analyses. State stuttering was associated with overactivation in the right hemisphere larynx and lip motor cortex. Trait stuttering was associated with overactivation of lip motor cortex in the right hemisphere but underactivation of larynx motor cortex in the left hemisphere. These results support a large literature highlighting laryngeal and lip involvement in the symptomatology of stuttering, and disambiguate two possible sources of activation in neuroimagingstudies of persistent developmental stuttering.

This paper demonstrates that in the treatment of psychiatric disorders, there are striking similarities between the mechanisms of psychoactive agents used in Traditional Chinese Medicine (TCM) and those of western psychopharmacology. While western researchers search for new treatments and novel mechanisms of action, investigators in Asia are analyzing traditional remedies in order to understand the mechanisms responsible for their effectiveness. A review of contemporary pharmacologic studies of agents used in TCM for psychiatric indications reveals that virtually all of the active principles of drug action established in 20th century psychopharmacology were encountered empirically in Chinese herbal medicine over the past 2000 years. Building bridges between these two traditions may thus be of benefit to both cultures. In addition to providing western patients with a wider selection of treatment options, the effort may help Asian clinicians and researchers avoid some of the errors that have troubled their western counterparts.

The amygdala plays a critical role in the neural system involved in emotional responses and conditioned fear. The dysfunction of this system is thought to be a cause of several neuropsychiatric disorders. A neuroimagingstudy provides a unique opportunity for noninvasive investigation of the human amygdala. We studied the activity of this structure in normal subjects and patients with schizophrenia by using the face recognition task. Our results showed that the amygdala was activated by presentation of face stimuli, and negative face activated the amygdala to a greater extent than a neutral face. Under the happy face condition, the activation of the amygdala was higher in the schizophrenic patients than in control subjects. A single nucleotide polymorphism in the regulatory region of the serotonin type 3 receptor gene had modulatory effects on the amygdaloid activity. The emotion regulation had a significant impact on neural interaction between the amygdala and prefrontal cortices. Thus, studies on the human amygdala would greatly contribute to the elucidation of the neural system that determines emotional and stress responses. To clarify the relevance of the neural dysfunction and neuropsychiatric disorders, further studies using physiological, genetic, and hormonal approaches are essential.

Significant resources around the world have been invested in neuroimagingstudies of brain function and disease. Easier access to this large body of work should have profound impact on research in cognitive neuroscience and psychiatry, leading to advances in the diagnosis and treatment of psychiatric and neurological disease. A trend toward increased sharing of neuroimaging data has emerged in recent years. Nevertheless, a number of barriers continue to impede momentum. Many researchers and institutions remain uncertain about how to share data or lack the tools and expertise to participate in data sharing. The use of electronic data capture (EDC) methods for neuroimaging greatly simplifies the task of data collection and has the potential to help standardize many aspects of data sharing. We review here the motivations for sharing neuroimaging data, the current data sharing landscape, and the sociological or technical barriers that still need to be addressed. The INCF Task Force on Neuroimaging Datasharing, in conjunction with several collaborative groups around the world, has started work on several tools to ease and eventually automate the practice of data sharing. It is hoped that such tools will allow researchers to easily share raw, processed, and derived neuroimaging data, with appropriate metadata and provenance records, and will improve the reproducibility of neuroimagingstudies. By providing seamless integration of data sharing and analysis tools within a commodity research environment, the Task Force seeks to identify and minimize barriers to data sharing in the field of neuroimaging. PMID:22493576

The restless legs syndrome (RLS) is a clinical diagnosis based on the four essential criteria defined by the International Restless Legs Syndrome Study Group (IRLSSG). An idiopathic form can be separated from a symptomatic form. Neurophysiological studies have investigated the pathophysiology of the idiopathic RLS or have been used to exclude a symptomatic cause, in particular polyneuropathy. So far cortical excitability changes, corticomotor, somatosensory and auditory pathways, spinal cord excitability, B-wave rhythm and cycling alternating pattern, as well as reflex mechanisms have been investigated by electroencephalography, evoked potentials, Bereitschaftspotentials, nerve conduction and thermal threshold measurements, electromyography, transcranial Doppler sonography, measurements of the spinal flexor reflex as well as neuroimaging techniques. The etiology of the RLS cannot be revealed by these methods, neurophysiological studies in RLS are, however, useful for a better understanding of the pathophysiology and for exclusion of a polyneuropathy or other symptomatic causes. In addition to neurophysiological investigations, small fiber neuropathy, which seems to be a more common finding in RLS patients than expected to date, may need biopsy for confirmation. This review will focus on investigations of the different systems involved with diverse neurophysiological methods.

Somatoform disorders (SD) are common medical disorders with prevalence rates between 3.5% and 18.4%, depending on country and medical setting. SD as outlined in the ICD-10 exhibits various biological, social, and psychological pathogenic factors. Little is known about the neural correlates of SD. The aims of this meta-analysis are to identify neuronal areas that are involved in SD and consistently differ between patients and healthy controls. We conducted a systematic literature research on neuroimagingstudies of SD. Ten out of 686 studies fulfilled the inclusion criteria and were analyzed using activation likelihood estimation. Five neuronal areas differ between patients with SD and healthy controls namely the premotor and supplementary motor cortexes, the middle frontal gyrus, the anterior cingulate cortex, the insula, and the posterior cingulate cortex. These areas seem to have a particular importance for the occurrence of SD. Out of the ten studies two did not contribute to any of the clusters. Our results seem to largely overlap with the circuit network model of somatosensory amplification for SD. It is conceivable that functional disorders, independent of the clinical impression, show similar neurobiological processes. While overlaps do occur it is necessary to understand single functional somatic syndromes and their aetiology for future research, terminology, and treatment guidelines. PMID:27182487

This study determined the involvement of women as first authors and other authors for every article published in Experimental and Clinical Psychopharmacology, Pharmacology Biochemistry and Behavior, and Psychopharmacology in 1991, 1996, 2001, and 2006. Their involvement as editors also was determined. Women's participation as authors, but not as editors, slightly increased over time. In 2006, 43% of first authors, 38% of other authors, and 24% of editors were women. The gender of subjects was examined for the same years and journals, but could not be determined for 6% and 9% of articles employing nonhuman and human subjects, respectively. In 2006, when subjects' gender could be determined, 77% of articles involving nonhuman subjects used only males, 9% only females, and 14% both males and females. In articles using human subjects in that same year, 17% involved only males, 6% only females, and 77% both males and females. Women researchers clearly make substantial contributions to the psychopharmacology literature, but are nonetheless underrepresented as editors. Findings regarding subjects indicate that there is growing recognition of the importance of gender as a determinant of drug effects, although the vast majority of nonhuman studies continue to involve only male subjects.

Neuroticism is a robust personality trait that constitutes a risk factor for mood disorders. Neuroimaging findings related to neuroticism have been inconsistent across studies and hardly integrated in order to construct a model of the underlying neural correlates of neuroticism. The aim of the current meta-analysis was to provide a quantitative summary of the literature, using a parametric coordinate-based meta-analysis (PCM) approach. Data were pooled for emotion processing tasks investigating the contrasts (negative>neutral) and (positive>neutral) to identify brain regions that are consistently associated with neuroticism across studies. Significant negative and positive correlations with neuroticism were found only for the contrast (negative>neutral) after multiple comparisons correction. Differences in brain activation were found to be associated with neuroticism during fear learning, anticipation of aversive stimuli and the processing and regulation of emotion. The relationship between neuroticism and these three psychological processes and their corresponding neural correlates is discussed. Furthermore, the meta-analytic findings are incorporated into a general model of emotion processing in neuroticism.

Although neuroimagingstudies strongly implicate the medial prefrontal cortex (ventral and dorsal), cingulate gyrus (anterior and posterior), precuneus and temporoparietal cortex in mediating self-referential processing (SRP), little is known about the neural bases mediating individual differences in valenced SRP, that is, processes intrinsic to self-esteem. This study investigated the neural correlates of experimentally engendered valenced SRP via the Visual–Verbal Self-Other Referential Processing Task in 20 women with fMRI. Participants viewed pictures of themselves or unknown other women during separate trials while covertly rehearsing ‘I am’ or ‘She is’, followed by reading valenced trait adjectives, thus variably associating the self/other with positivity/negativity. Response within dorsal and ventral medial prefrontal cortex, cingulate cortex and left temporoparietal cortex varied with individual differences in both pre-task rated self-descriptiveness of the words, as well as task-induced affective responses. Results are discussed as they relate to a social cognitive and affective neuroscience view of self-esteem. PMID:22403154

Posttraumatic stress disorder (PTSD) is a psychiatric syndrome that develops after exposure to terrifying and life-threatening events including warfare, motor-vehicle accidents, and physical and sexual assault. The emotional experience of psychological trauma can have long-term cognitive effects. The hallmark symptoms of PTSD involve alterations to cognitive processes such as memory, attention, planning, and problem solving, underscoring the detrimental impact that negative emotionality has on cognitive functioning. As such, an important challenge for PTSD researchers and treatment providers is to understand the dynamic interplay between emotion and cognition. Contemporary cognitive models of PTSD theorize that a preponderance of information processing resources are allocated toward threat detection and interpretation of innocuous stimuli as threatening, narrowing one's attentional focus at the expense of other cognitive operations. Decades of research have shown support for these cognitive models of PTSD using a variety of tasks and methodological approaches. The primary goal of this review is to summarize the latest neurocognitive and neuroimaging research of emotion-cognition interactions in PTSD. To directly assess the influence of emotion on cognition and vice versa, the studies reviewed employed challenge tasks that included both cognitive and emotional components. The findings provide evidence for memory and attention deficits in PTSD that are often associated with changes in functional brain activity. The results are reviewed to provide future directions for research that may direct better and more effective treatments for PTSD. PMID:23087624

Social cognition includes various components of information processing related to communication with other individuals. In this review, we have discussed 3 components of social cognitive function: face recognition, empathy, and decision making. Our social behavior involves recognition based on facial features and also involves empathizing with others; while making decisions, it is important to consider the social consequences of the course of action followed. Face recognition is divided into 2 routes for information processing: a route responsible for overt recognition of the face's identity and a route for emotional and orienting responses based on the face's personal affective significance. Two systems are possibly involved in empathy: a basic emotional contagion "mirroring" system and a more advanced "theory of mind" system that considers the cognitive perspective. Decision making is mediated by a widespread system that includes several cortical and subcortical components. Numerous lesion and neuroimagingstudies have contributed to clarifying the neural correlates of social cognitive function, and greater information can be obtained on social cognitive function by combining these 2 approaches.

Neuroimaging research has begun to unveil the mechanisms behind emotion processing during the postpartum period, which, in turn, may be of relevance for the development of postpartum depression. The present study sought to longitudinally investigate the neural correlates of emotion anticipation during the postpartum period in healthy women. Functional magnetic resonance imaging was employed to measure the blood oxygen level-dependent signal in the brain in response to anticipation of negative emotional stimuli and during processing of images with positive or negative valence. The participating women were scanned twice: the first scan occurred during the first 48 hours after delivery, and the second was performed 4-6 weeks after delivery. The early postpartum period was characterized by higher anterior cingulate cortex reactivity during anticipation of negative emotional stimuli than the late postpartum period. This was accompanied by a negative relationship with insular reactivity during the early postpartum period and a trend towards an increase in insular reactivity in the late postpartum period. Thus, during the first four weeks of the postpartum period, a diminished top-down regulatory feedback on emotion-related areas of the brain was noted. This finding suggests a physiologically important adaptation during the healthy postpartum period.

Brain damage can cause remarkably selective deficits in processing specific categories of objects, indicating the high degree of functional segregation within the brain. The neuroimagingstudy presented here investigates differences in the neural activity associated with two categories of natural objects (animals and fruit) and two categories of man-made objects (vehicles and tools). Stimuli were outline drawings and the tasks were naming and word-picture matching. For man-made objects, the only category-specific effect was in the left posterior middle temporal cortex, which was most active for drawings of tools, as previously reported. For natural objects, drawings of animals and fruit (relative to drawings of man-made objects) enhanced activity in bilateral anterior temporal and right posterior middle temporal cortices. Critically, these effects with natural objects were not observed when the stimuli were coloured appropriately to facilitate identification. Furthermore, activation in the same right hemisphere areas was also observed for viewing and matching unfamiliar non-objects relative to naming and matching man-made objects. These results indicate that, in the right hemisphere, differences between processing natural relative to man-made objects overlap with the effects of increasing demands on object identification. In the left hemisphere, the effects are more consistent with functional specialization within the semantic system. We discuss (i) how category-specific differences can emerge for multiple reasons and (ii) the implications of these effects on the interpretation of functional imaging data and patients with category-specific deficits.

Published studies using functional and structural MRI include many errors in the way data are analyzed and conclusions reported. This was observed when working on a comprehensive review of the neural bases of synesthesia, but these errors are probably endemic to neuroimagingstudies. All studies reviewed had based their conclusions using Null Hypothesis Significance Tests (NHST). NHST have yet been criticized since their inception because they are more appropriate for taking decisions related to a Null hypothesis (like in manufacturing) than for making inferences about behavioral and neuronal processes. Here I focus on a few key problems of NHST related to brain imaging techniques, and explain why or when we should not rely on “significance” tests. I also observed that, often, the ill-posed logic of NHST was even not correctly applied, and describe what I identified as common mistakes or at least problematic practices in published papers, in light of what could be considered as the very basics of statistical inference. MRI statistics also involve much more complex issues than standard statistical inference. Analysis pipelines vary a lot between studies, even for those using the same software, and there is no consensus which pipeline is the best. I propose a synthetic view of the logic behind the possible methodological choices, and warn against the usage and interpretation of two statistical methods popular in brain imaging studies, the false discovery rate (FDR) procedure and permutation tests. I suggest that current models for the analysis of brain imaging data suffer from serious limitations and call for a revision taking into account the “new statistics” (confidence intervals) logic. PMID:25745383

In this study, an activation likelihood estimation (ALE) meta-analysis was used to conduct a quantitative investigation of neuroimagingstudies on divergent thinking. Based on the ALE results, the functional magnetic resonance imaging (fMRI) studies showed that distributed brain regions were more active under divergent thinking tasks (DTTs) than those under control tasks, but a large portion of the brain regions were deactivated. The ALE results indicated that the brain networks of the creative idea generation in DTTs may be composed of the lateral prefrontal cortex, posterior parietal cortex [such as the inferior parietal lobule (BA 40) and precuneus (BA 7)], anterior cingulate cortex (ACC) (BA 32), and several regions in the temporal cortex [such as the left middle temporal gyrus (BA 39), and left fusiform gyrus (BA 37)]. The left dorsolateral prefrontal cortex (BA 46) was related to selecting the loosely and remotely associated concepts and organizing them into creative ideas, whereas the ACC (BA 32) was related to observing and forming distant semantic associations in performing DTTs. The posterior parietal cortex may be involved in the semantic information related to the retrieval and buffering of the formed creative ideas, and several regions in the temporal cortex may be related to the stored long-term memory. In addition, the ALE results of the structural studies showed that divergent thinking was related to the dopaminergic system (e.g., left caudate and claustrum). Based on the ALE results, both fMRI and structural MRI studies could uncover the neural basis of divergent thinking from different aspects (e.g., specific cognitive processing and stable individual difference of cognitive capability).

Background Biomonitoring is a critical tool to assess the effects of chemicals on health, as scientists seek to better characterize life-course exposures from diverse environments. This trend, coupled with increased institutional support for community-engaged environmental health research, challenge established ethical norms related to biomonitoring results communication and data sharing between scientists, study participants, and their wider communities. Methods Through a literature review, participant observation at workshops, and interviews, we examine ethical tensions related to reporting individual data from chemical biomonitoring studies by drawing relevant lessons from the genetics and neuroimaging fields. Results In all three fields ethical debates about whether/how to report-back results to study participants are precipitated by two trends. First, changes in analytical methods have made more data accessible to stakeholders. For biomonitoring, improved techniques enable detection of more chemicals at lower levels, and diverse groups of scientists and health advocates now conduct exposure studies. Similarly, innovations in genetics have catalyzed large-scale projects and broadened the scope of who has access to genetic information. Second, increasing public interest in personal medical information has compelled imaging researchers to address demands by participants to know their personal data, despite uncertainties about their clinical significance. Four ethical arenas relevant to biomonitoring results communication emerged from our review: Tensions between participants’ right-to-know their personal results versus their ability or right-to-act to protect their health; whether and how to report incidental findings; informed consent in biobanking; and open-access data sharing. Conclusion Ethically engaging participants in biomonitoring studies requires consideration of several issues, including scientific uncertainty about health implications and exposure

The striatum has traditionally mainly been associated with playing a key role in the modulation of motor functions. Indeed, lesion studies in animals and studies of some neurological conditions in humans have brought further evidence to this idea. However, better methods of investigation have raised concerns about this notion, and it was proposed that the striatum could also be involved in different types of functions including cognitive ones. Although the notion was originally a matter of debate, it is now well-accepted that the caudate nucleus contributes to cognition, while the putamen could be involved in motor functions, and to some extent in cognitive functions as well. With the arrival of modern neuroimaging techniques in the early 1990, knowledge supporting the cognitive aspect of the striatum has greatly increased, and a substantial number of scientific papers were published studying the role of the striatum in healthy individuals. For the first time, it was possible to assess the contribution of specific areas of the brain during the execution of a cognitive task. Neuroanatomical studies have described functional loops involving the striatum and the prefrontal cortex suggesting a specific interaction between these two structures. This review examines the data up to date and provides strong evidence for a specific contribution of the fronto-striatal regions in different cognitive processes, such as set-shifting, self-initiated responses, rule learning, action-contingency, and planning. Finally, a new two-level functional model involving the prefrontal cortex and the dorsal striatum is proposed suggesting an essential role of the dorsal striatum in selecting between competing potential responses or actions, and in resolving a high level of ambiguity. PMID:26500513

This case study describes 1 year of the psychoanalytic psychotherapy using clinical data, a standardized instrument of the psychotherapeutic process (Psychotherapy process Q-Set, PQS), and functional neuroimaging (fMRI). A female dysthymic patient with narcissistic traits was assessed at monthly intervals (12 sessions). In the fMRI scans, which took place immediately after therapy hours, the patient looked at pictures of attachment-relevant scenes (from the Adult Attachment Projective Picture System, AAP) divided into two groups: those accompanied by a neutral description, and those accompanied by a description tailored to core conflicts of the patient as assessed in the AAP. Clinically, this patient presented defense mechanisms that influenced the relationship with the therapist and that was characterized by fluctuations of mood that lasted whole days, following a pattern that remained stable during the year of the study. The two modes of functioning associated with the mood shifts strongly affected the interaction with the therapist, whose quality varied accordingly (“easy” and “difficult” hours). The PQS analysis showed the association of “easy” hours with the topic of the involvement in significant relationships and of “difficult hours” with self-distancing, a defensive maneuver common in narcissistic personality structures. In the fMRI data, the modes of functioning visible in the therapy hours were significantly associated with modulation of the signal elicited by personalized attachment-related scenes in the posterior cingulate (p = 0.017 cluster-level, whole-volume corrected). This region has been associated in previous studies to self-distancing from negatively valenced pictures presented during the scan. The present study may provide evidence of the possible involvement of this brain area in spontaneously enacted self-distancing defensive strategies, which may be of relevance in resistant reactions in the course of a psychoanalytic

Parenting behavior critically shapes human infants’ current and future behavior. The parent–infant relationship provides infants with their first social experiences, forming templates of what they can expect from others and how to best meet others’ expectations. In this review, we focus on the neurobiology of parenting behavior, including our own functional magnetic resonance imaging (fMRI) brain imaging experiments of parents. We begin with a discussion of background, perspectives and caveats for considering the neurobiology of parent–infant relationships. Then, we discuss aspects of the psychology of parenting that are significantly motivating some of the more basic neuroscience research. Following that, we discuss some of the neurohormones that are important for the regulation of social bonding, and the dysregulation of parenting with cocaine abuse. Then, we review the brain circuitry underlying parenting, proceeding from relevant rodent and nonhuman primate research to human work. Finally, we focus on a study-by-study review of functional neuroimagingstudies in humans. Taken together, this research suggests that networks of highly conserved hypothalamic–midbrain–limbic–paralimbic–cortical circuits act in concert to support aspects of parent response to infants, including the emotion, attention, motivation, empathy, decision-making and other thinking that are required to navigate the complexities of parenting. Specifically, infant stimuli activate basal forebrain regions, which regulate brain circuits that handle specific nurturing and caregiving responses and activate the brain’s more general circuitry for handling emotions, motivation, attention, and empathy – all of which are crucial for effective parenting. We argue that an integrated understanding of the brain basis of parenting has profound implications for mental health. PMID:17355399

Vestibular neuritis (VN) is one of the most common causes of vertigo and is characterised by a sudden unilateral vestibular failure (UVF). Many neuroimagingstudies in the last 10 years have focused on brain changes related to sudden vestibular deafferentation as in VN. However, most of these studies, also due to different possibilities across diverse centres, were based on different times of first acquisition from the onset of VN symptoms, neuroimaging techniques, statistical analysis and correlation with otoneurological and psychological findings. In the present review, the authors aim to merge together the similarities and discrepancies across various investigations that have employed neuroimaging techniques and group analysis with the purpose of better understanding about how the brain changes and what characteristic clinical features may relate to each other in the acute phase of VN. Six studies that strictly met inclusion criteria were analysed to assess cortical-subcortical correlates of acute clinical features related to VN. The present review clearly reveals that sudden UVF may induce a wide variety of cortical and subcortical responses - with changes in different sensory modules - as a result of acute plasticity in the central nervous system.

Pharmacological challenge in conjunction with neuroimaging techniques has been employed for over two decades now to understand the neural basis of the cognitive, emotional and symptomatic effects of the main ingredients of cannabis, the most widely used illicit drug in the world. This selective critical review focuses on the human neuroimagingstudies investigating the effects of delta-9- tetrahydrocannabinol (THC) and cannabidiol (CBD), the two main cannabinoids of interest present in the extract of the cannabis plant. These studies suggest that consistent with the polymorphic and heterogeneous nature of the effects of cannabis, THC and CBD have distinct and often opposing effects on widely distributed neural networks that include medial temporal and prefrontal cortex and striatum, brain regions that are rich in cannabinoid receptors and implicated in the pathophysiology of psychosis. They help elucidate the neurocognitive mechanisms underlying the acute induction of psychotic symptoms by cannabis and provide mechanistic understanding underlying the potential role of CBD as an anxiolytic and antipsychotic. Although there are ethical and methodological caveats, pharmacological neuroimagingstudies such as those reviewed here may not only help model different aspects of the psychopathology of mental disorders such as schizophrenia and offer insights into their underlying mechanisms, but may suggest potentially new therapeutic targets for drug discovery.

One of the major challenges within Optical Imaging, photon propagation through clear layers embedded between scattering tissues, can be now efficiently modelled in real-time thanks to the Monte Carlo approach based on GPU. Because of its nature, the photon propagation problem can be very easily parallelized and ran on low cost hardware, avoiding the need for expensive Super Computers. A comparison between Diffusion and MC photon propagation theory is presented in this work with application to neuroimaging, investigating low scattering regions in a mouse-like phantom. Regions such as the Cerebral Spinal Fluid, are currently not taken into account in the classical computational models because of the impossibility to accurately simulate light propagation using fast Diffusive Equation approaches, leading to inaccuracies during the reconstruction process. The goal of the study presented here, is to reduce and further improve the computation accuracy of the reconstructed solution in a highly realistic scenario in the case of neuroimaging in preclinical mouse models.

We performed an updated quantitative meta-analysis of 162 neuroimagingstudies of emotion using a novel multi-level kernel-based approach, focusing on locating brain regions consistently activated in emotional tasks and their functional organization into distributed functional groups, independent of semantically defined emotion category labels (e.g., “anger,” “fear”). Such brain-based analyses are critical if our ways of labeling emotions are to be evaluated and revised based on consistency with brain data. Consistent activations were limited to specific cortical sub-regions, including multiple functional areas within medial, orbital, and inferior lateral frontal cortices. Consistent with a wealth of animal literature, multiple subcortical activations were identified, including amygdala, ventral striatum, thalamus, hypothalamus, and periaqueductal gray. We used multivariate parcellation and clustering techniques to identify groups of co-activated brain regions across studies. These analyses identified six distributed functional groups, including medial and lateral frontal groups, two posterior cortical groups, and paralimbic and core limbic/brainstem groups. These functional groups provide information on potential organization of brain regions into large-scale networks. Specific follow-up analyses focused on amygdala, periaqueductal gray (PAG), and hypothalamic (Hy) activations, and identified frontal cortical areas co-activated with these core limbic structures. While multiple areas of frontal cortex co-activated with amygdala sub-regions, a specific region of dorsomedial prefrontal cortex (dmPFC, Brodmann’s Area 9/32) was the only area co-activated with both PAG and Hy. Subsequent mediation analyses were consistent with a pathway from dmPFC through PAG to Hy. These results suggest that medial frontal areas are more closely associated with core limbic activation than their lateral counterparts, and that dmPFC may play a particularly important role in the

Background Oral-facial-digital type 1 syndrome (OFD1; OMIM 311200) belongs to the expanding group of disorders ascribed to ciliary dysfunction. With the aim of contributing to the understanding of the role of primary cilia in the central nervous system (CNS), we performed a thorough characterization of CNS involvement observed in this disorder. Methods A cohort of 117 molecularly diagnosed OFD type I patients was screened for the presence of neurological symptoms and/or cognitive/behavioral abnormalities on the basis of the available information supplied by the collaborating clinicians. Seventy-one cases showing CNS involvement were further investigated through neuroimagingstudies and neuropsychological testing. Results Seventeen patients were molecularly diagnosed in the course of this study and five of these represent new mutations never reported before. Among patients displaying neurological symptoms and/or cognitive/behavioral abnormalities, we identified brain structural anomalies in 88.7%, cognitive impairment in 68%, and associated neurological disorders and signs in 53% of cases. The most frequently observed brain structural anomalies included agenesis of the corpus callosum and neuronal migration/organisation disorders as well as intracerebral cysts, porencephaly and cerebellar malformations. Conclusions Our results support recent published findings indicating that CNS involvement in this condition is found in more than 60% of cases. Our findings correlate well with the kind of brain developmental anomalies described in other ciliopathies. Interestingly, we also described specific neuropsychological aspects such as reduced ability in processing verbal information, slow thought process, difficulties in attention and concentration, and notably, long-term memory deficits which may indicate a specific role of OFD1 and/or primary cilia in higher brain functions. PMID:24884629

The aim of this study was to characterize the neuropsychological and neuroimaging profiles of mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients, and to study the magnitude of the differences by comparing both outcomes with healthy subjects in a cross-sectional manner. Five hundred and thirty-five subjects (356 cognitively normal adults (CONT), 79 MCI, and 100 AD) were assessed with the NEURONORMA neuropsychological battery. Thirty CONT, 23 MCI, and 23 AD subjects from this sample were included in the neuroimaging substudy. Patients' raw cognitive scores were converted to age and education-adjusted scaled ones (range 2-18) using co-normed reference values. Medians were plotted to examine the cognitive profile. MRIs were processed by means of FreeSurfer. Effect size indices (Cohen's d) were calculated in order to compare the standardized differences between patients and healthy subjects. Graphically, the observed cognitive profiles for MCI and AD groups produced near to parallel lines. Verbal and visual memories were the most impaired domains in both groups, followed by executive functions and linguistic/semantic ones. The largest effect size between AD and cognitively normal subjects was found for the FCSRT (d = 4.05, AD versus CONT), which doubled the value obtained by the best MRI measure, the right hippocampus (d = 1.65, AD versus CONT). Our results support the notion of a continuum in cognitive profile between MCI and AD. Neuropsychological outcomes, in particular the FCSRT, are better than neuroimaging ones at detecting differences among subjects.

Purpose To evaluate pathways through which sociodemographic, clinical, attitudinal, and perceived health control variables impact psychiatric patients’ adherence to psychopharmacological medications. Method A sample of 966 consecutive psychiatric outpatients was studied. The variables were sociodemographic (age, gender, and education), clinical (diagnoses, drug treatment, and treatment duration), attitudinal (attitudes toward psychopharmacological medication and preferences regarding participation in decision-making), perception of control over health (health locus of control, self-efficacy, and psychological reactance), and level of adherence to psychopharmacological medications. Structural equation modeling was applied to examine the nonstraightforward relationships and the interactive effects among the analyzed variables. Results Structural equation modeling demonstrated that psychiatric patients’ treatment adherence was associated: 1) negatively with cognitive psychological reactance (adherence decreased as cognitive psychological reactance increased), 2) positively with patients’ trust in their psychiatrists (doctors’ subscale), 3) negatively with patients’ belief that they are in control of their mental health and that their mental health depends on their own actions (internal subscale), and 4) positively (although weakly) with age. Self-efficacy indirectly influenced treatment adherence through internal health locus of control. Conclusion This study provides support for the hypothesis that perceived health control variables play a relevant role in psychiatric patients’ adherence to psychopharmacological medications. The findings highlight the importance of considering prospective studies of patients’ psychological reactance and health locus of control as they may be clinically relevant factors contributing to adherence to psychopharmacological medications.

From the very outset of scientific Psychology, psychologists have shown interest for drugs and their effects on behavior. This has given rise to numerous contributions, mostly in the form of Psychopharmacology publications. The aim of this study was to quantitatively evaluate these contributions and compare them with other academic disciplines related to Psychopharmacology. Using the PubMed database, we retrieved information about articles from 15 journals included in the Pharmacology and Pharmacy category of the Journal Citation Reports database for a 21-year period (1987 to 2007). There were 37540 articles which about 52% were represented by 3 journals. About 70% of psychology publications were represented by 2 of these journals. Psychology departments accounted for the 11% of the published papers, which places Psychology third behind Psychiatry and Pharmacology, which contributed to 22.69 and 13% respectively. Psychology contributed to the greatest number of studies in 3 journals, second in 3 and third in 8. This report represents the first effort to explore the contribution of academic Psychology to the multidisciplinary science of psychopharmacology. Although leaders of production of psychopharmacology research were from Psychiatry and Pharmacology, Psychology departments are an important source of studies and thus of knowledge in the field of Psychopharmacology.

The best available evidence for psychopharmacologic treatment of borderline personality disorder (BPD) is outlined here. BPD is defined by disturbances in identity and interpersonal functioning, and patients report potential medication treatment targets such as impulsivity, aggression, transient psychotic and dissociative symptoms, and refractory affective instability Few randomized controlled trials of psychopharmacological treatments for BPD have been published recently, although multiple reviews have converged on the effectiveness of specific anticonvulsants, atypical antipsychotic agents, and omega-3 fatty acid supplementation. Stronger evidence exists for medication providing significant improvements in impulsive aggression than in affective or other interpersonal symptoms. Future research strategies will focus on the potential role of neuropeptide agents and medications with greater specificity for 2A serotonin receptors, as well as optimizing concomitant implementation of evidence-based psychotherapy and psychopharmacology, in order to improve BPD patients' overall functioning.

Although cerebral palsy (CP) is among the most common causes of physical disability in early childhood, we know little about the functional and structural changes of this disorder in the developing brain. Here, we investigated with three different neuroimaging modalities [magnetoencephalography (MEG), diffusion tensor imaging (DTI), and resting-state fMRI] whether spastic CP is associated with functional and anatomical abnormalities in the sensorimotor network. Ten children participated in the study: four with diplegic CP (DCP), three with hemiplegic CP (HCP), and three typically developing (TD) children. Somatosensory (SS)-evoked fields (SEFs) were recorded in response to pneumatic stimuli applied to digits D1, D3, and D5 of both hands. Several parameters of water diffusion were calculated from DTI between the thalamus and the pre-central and post-central gyri in both hemispheres. The sensorimotor resting-state networks (RSNs) were examined by using an independent component analysis method. Tactile stimulation of the fingers elicited the first prominent cortical response at ~50 ms, in all except one child, localized over the primary SS cortex (S1). In five CP children, abnormal somatotopic organization was observed in the affected (or more affected) hemisphere. Euclidean distances were markedly different between the two hemispheres in the HCP children, and between DCP and TD children for both hemispheres. DTI analysis revealed decreased fractional anisotropy and increased apparent diffusion coefficient for the thalamocortical pathways in the more affected compared to less affected hemisphere in CP children. Resting-state functional MRI results indicated absent and/or abnormal sensorimotor RSNs for children with HCP and DCP consistent with the severity and location of their lesions. Our findings suggest an abnormal SS processing mechanism in the sensorimotor network of children with CP possibly as a result of diminished thalamocortical projections. PMID:25309398

Psychopharmacologic treatment is playing a greater role in the management of patients with eating disorders. In this paper, we review randomized, placebo-controlled trials (RCTs) conducted in anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), and other eating disorders over the past 3 years. Fluoxetine remains the only medication approved for an eating disorder, that being BN. RCTs of antipsychotics in AN have had mixed results; the only agent with some evidence of efficacy is olanzapine. One study suggests dronabinol may induce weight gain in AN. Preliminary studies suggest lack of efficacy of alprazolam, dehydroepiandrosterone, or physiologic estrogen replacement in AN; erythromycin in BN; and the opioid antagonist ALKS-33 in BED. In BED with obesity or overweight, bupropion may cause mild weight loss without seizures, and chromium may improve glucose regulation. Also in BED, three RCTs suggest the stimulant prodrug lisdexamfetamine may reduce binge eating episodes, and another RCT suggests intranasal naloxone may decrease time spent binge eating. There remains a disconnection between the size of eating disorders as a public health problem and the lack of pharmacotherapy research of these conditions.

This commentary focuses on psychopharmacology teachers and their teaching. The authors offer broadly based pedagogic suggestions on how to deliver evidence-based and neurobiologically informed prescribing information to clinicians at all levels of experience. They argue that teaching essential psychopharmacology knowledge and practice must be up-to-date, accurate, and consistent with the reality of an individual patient's life experience and beliefs. They stress that educators must teach that nonpsychopharmacological factors in a patient's life may be as relevant to the treatment setting as the actual pharmacological basis of psychotropic drug therapeutics.

Rapid advances in neuroscience and clinical research have made the practice of quality clinical psychopharmacology increasingly difficult. While practice guidelines, model psychopharmacology curricula, and clinical algorithms have helped "the science" of psychopharmacology, they often fail to provide guidance for clinicians in specific clinical situations with individual patients. Quality psychopharmacology practice is based on a combination of knowledge, experience, judgment, and luck. In this article, the authors present their collection of psychopharmacology "pearls" for trainees as well as experienced clinicians. (Journal of Psychiatric Practice 2009;15:423-426).

Neuroimagingstudies have gained increasing importance in validating neurobiological network hypotheses for anxiety disorders. Functional imaging procedures and radioligand binding studies in healthy subjects and in patients with anxiety disorders provide growing evidence of the existence of a complex anxiety network, including limbic, brainstem, temporal, and prefrontal cortical regions. Obviously, "normal anxiety" does not equal "pathological anxiety" although many phenomena are evident in healthy subjects, however to a lower extent. Differential effects of distinct brain regions and lateralization phenomena in different anxiety disorders are mentioned. An overview of neuroimaging investigations in anxiety disorders is given after a brief summary of results from healthy volunteers. Concluding implications for future research are made by the authors.

OpenMOLE is a scientific workflow engine with a strong emphasis on workload distribution. Workflows are designed using a high level Domain Specific Language (DSL) built on top of Scala. It exposes natural parallelism constructs to easily delegate the workload resulting from a workflow to a wide range of distributed computing environments. OpenMOLE hides the complexity of designing complex experiments thanks to its DSL. Users can embed their own applications and scale their pipelines from a small prototype running on their desktop computer to a large-scale study harnessing distributed computing infrastructures, simply by changing a single line in the pipeline definition. The construction of the pipeline itself is decoupled from the execution context. The high-level DSL abstracts the underlying execution environment, contrary to classic shell-script based pipelines. These two aspects allow pipelines to be shared and studies to be replicated across different computing environments. Workflows can be run as traditional batch pipelines or coupled with OpenMOLE's advanced exploration methods in order to study the behavior of an application, or perform automatic parameter tuning. In this work, we briefly present the strong assets of OpenMOLE and detail recent improvements targeting re-executability of workflows across various Linux platforms. We have tightly coupled OpenMOLE with CARE, a standalone containerization solution that allows re-executing on a Linux host any application that has been packaged on another Linux host previously. The solution is evaluated against a Python-based pipeline involving packages such as scikit-learn as well as binary dependencies. All were packaged and re-executed successfully on various HPC environments, with identical numerical results (here prediction scores) obtained on each environment. Our results show that the pair formed by OpenMOLE and CARE is a reliable solution to generate reproducible results and re-executable pipelines. A

OpenMOLE is a scientific workflow engine with a strong emphasis on workload distribution. Workflows are designed using a high level Domain Specific Language (DSL) built on top of Scala. It exposes natural parallelism constructs to easily delegate the workload resulting from a workflow to a wide range of distributed computing environments. OpenMOLE hides the complexity of designing complex experiments thanks to its DSL. Users can embed their own applications and scale their pipelines from a small prototype running on their desktop computer to a large-scale study harnessing distributed computing infrastructures, simply by changing a single line in the pipeline definition. The construction of the pipeline itself is decoupled from the execution context. The high-level DSL abstracts the underlying execution environment, contrary to classic shell-script based pipelines. These two aspects allow pipelines to be shared and studies to be replicated across different computing environments. Workflows can be run as traditional batch pipelines or coupled with OpenMOLE's advanced exploration methods in order to study the behavior of an application, or perform automatic parameter tuning. In this work, we briefly present the strong assets of OpenMOLE and detail recent improvements targeting re-executability of workflows across various Linux platforms. We have tightly coupled OpenMOLE with CARE, a standalone containerization solution that allows re-executing on a Linux host any application that has been packaged on another Linux host previously. The solution is evaluated against a Python-based pipeline involving packages such as scikit-learn as well as binary dependencies. All were packaged and re-executed successfully on various HPC environments, with identical numerical results (here prediction scores) obtained on each environment. Our results show that the pair formed by OpenMOLE and CARE is a reliable solution to generate reproducible results and re-executable pipelines. A

An approach to the use of computer assisted instruction (CAI) for teaching psychopharmacology is presented. A project is described in which, using the TUTOR programing language on the PLATO IV computer system, several computer programs were developed to demonstrate the concepts of aminergic transmitters in the central nervous system. Response…

The editors of Pharmacopsychiatry have decided in 2016 to prepare special issues regularly in order provide our readers volumes of the journal with a thematic focus 1. The first such special issue is dedicated to the field of child and adolescent psychopharmacology. Many young patients are treated with psychotherapeutic, but also pharmacotherapeutic, methods worldwide. Most of our psychopharmacological agents are not approved by the federal institutions for persons under 18 years old. However, severe mental illnesses like schizophrenia, depression, anxiety, ADHD, and bipolar disorder frequently require pharmacological treatments in children and adolescents. We also see a wide range of rather unspecific emotional and behavioral disturbances up to excitation crises or suicidal acts in this young population, so that we see the necessity for standardized and valid psychopharmacological treatment regimens based on meta-analyses, randomized controlled trials, and guidelines 2. Child and adolescent psychiatry is unfortunately far away from this; industry-supported research is rare in this area, but also not all child and adolescent psychiatrists see the importance of psychopharmacological treatment and trust specific psychotherapy, psychoeducation, and educational strategies. These are all extremely important treatments, but one can/should think that psychopharmacotherapy is an important addition and often a cornerstone for the other treatments.

Objective: Psychiatrists and other physicians sometimes read publications superficially, relying excessively on abstracts. The authors addressed this problem by teaching critical appraisal of individual articles. Method: The authors developed a 23-item appraisal instrument to assess articles in the area of psychopharmacology. The results were…

Background Life trauma is highly prevalent in the general population and posttraumatic stress disorder is among the most prevalent psychiatric consequences of trauma exposure. Brazil has a unique environment to conduct translational research about psychological trauma and posttraumatic stress disorder, since urban violence became a Brazilian phenomenon, being particularly related to the rapid population growth of its cities. This research involves three case-control studies: a neuropsychological, a structural neuroimaging and a molecular neuroimagingstudy, each focusing on different objectives but providing complementary information. First, it aims to examine cognitive functioning of PTSD subjects and its relationships with symptomatology. The second objective is to evaluate neurostructural integrity of orbitofrontal cortex and hippocampus in PTSD subjects. The third aim is to evaluate if patients with PTSD have decreased dopamine transporter density in the basal ganglia as compared to resilient controls subjects. This paper shows the research rationale and design for these three case-control studies. Methods and design Cases and controls will be identified through an epidemiologic survey conducted in the city of São Paulo. Subjects exposed to traumatic life experiences resulting in posttraumatic stress disorder (cases) will be compared to resilient victims of traumatic life experiences without PTSD (controls) aiming to identify biological variables that might protect or predispose to PTSD. In the neuropsychological case-control study, 100 patients with PTSD, will be compared with 100 victims of trauma without posttraumatic stress disorder, age- and sex-matched controls. Similarly, 50 cases and 50 controls will be enrolled for the structural study and 25 cases and 25 controls in the functional neuroimagingstudy. All individuals from the three studies will complete psychometrics and a structured clinical interview (the Structured Clinical Interview for DSM-IV and

Technological advances in neuroimaging have enabled researchers to examine, in vivo, the relationship between psychotherapeutic interventions and markers of brain activity. This review focuses on two kinds of neuroimagingstudies in psychotherapy: those that examine the patterns of brain activity associated with response to treatments and those that examine the changes that occur in brain activity during treatment. A general, hypothetical neural model of psychotherapy is presented, and support for the model is evaluated across anxiety disorders and major depression. Neuroimagingstudies are broadly consistent in observing associations between response to psychotherapy and baseline activity in several key regions within the prefrontal cortex, basal ganglia, and limbic areas. These regions are involved in the generation and regulation of emotion, fear responding, and response to reward. Pre-post examinations of change following psychotherapy also typically observe that psychological treatments for anxiety and depression can affect neural activity in these regions. Despite general consensus that activity in these regions is associated with psychotherapy, substantial discrepancy persists regarding the precise direction of the observed relationships. Methodological challenges of the existing literature are considered, and future directions are discussed. PMID:25346646

Timing and other cognitive processes demanding cognitive control become interlinked when there is an increase in the level of difficulty or effort required. Both functions are interrelated and share neuroanatomical bases. A previous meta-analysis of neuroimagingstudies found that people with schizophrenia had significantly lower activation, relative to normal controls, of most right hemisphere regions of the time circuit. This finding suggests that a pattern of disconnectivity of this circuit, particularly in the supplementary motor area, is a trait of this mental disease. We hypothesize that a dysfunctional temporal/cognitive control network underlies both cognitive and psychiatric symptoms of schizophrenia and that timing dysfunction is at the root of the cognitive deficits observed. The goal of our study was to look, in schizophrenia patients, for brain structures activated both by execution of cognitive tasks requiring increased effort and by performance of time perception tasks. We conducted a signed differential mapping (SDM) meta-analysis of functional neuroimagingstudies in schizophrenia patients assessing the brain response to increasing levels of cognitive difficulty. Then, we performed a multimodal meta-analysis to identify common brain regions in the findings of that SDM meta-analysis and our previously-published activation likelihood estimate (ALE) meta-analysis of neuroimaging of time perception in schizophrenia patients. The current study supports the hypothesis that there exists an overlap between neural structures engaged by both timing tasks and non-temporal cognitive tasks of escalating difficulty in schizophrenia. The implication is that a deficit in timing can be considered as a trait marker of the schizophrenia cognitive profile. PMID:26925013

The neural basis of auditory object processing in the human cerebral cortex was investigated by combining neural modeling and functional neuroimaging. We developed a large-scale, neurobiologically realistic network model of auditory pattern recognition that relates neuronal dynamics of cortical auditory processing of frequency-modulated (FM) sweeps to functional neuroimaging data obtained using functional magnetic resonance imaging (fMRI). FM sweeps are ubiquitous in animal communication. Areas included in the model extend from primary auditory to prefrontal cortex. The electrical activities of the model neuronal units were constrained to agree with data from the neurophysiological literature regarding FM sweep perception. A fMRI experiment using stimuli and tasks similar to those used in our simulations was performed. The regional integrated synaptic activities of the model were used to determine simulated regional fMRI activities, and generally agreed with the experimentally observed fMRI data. Our results demonstrate that the model is capable of exhibiting the salient features of both electrophysiological neuronal activities and fMRI values that are in agreement with empirically observed data. These findings provide support for our hypotheses concerning how auditory objects are processed by primate neocortex. This type of approach offers the potential for understanding the neural basis of human speech perception.

Neuroimaging investigations have identified the neural correlates of reappraisal in executive areas. These findings have been interpreted as evidence for recruitment of controlled processes, at the expense of automatic processes when responding to emotional stimuli. However, activation of semantic areas has also been reported. The aim of the present work was to address the issue of the importance of semantic areas in emotion regulation by comparing recruitment of executive and semantic neural substrates in studies investigating different reappraisal strategies. With this aim, we reviewed neuroimagingstudies on reappraisal and we classified them in two main categories: reappraisal of stimuli (RS) and reappraisal via perspective taking (RPT). We applied a coordinate-based meta-analysis to summarize the results of fMRI studies on different reappraisal strategies. Our results showed that reappraisal, when considered regardless of the specific instruction used in the studies, involved both executive and semantic areas of the brain. When considering different reappraisal strategies separately, in contrast, we found areas associated with executive function to be prominently recruited by RS, even if also semantic areas were activated. Instead, in RPT the most important clusters of brain activity were found in parietal and temporal semantic areas, without significant clusters in executive areas. These results indicate that modulation of activity in semantic areas may constitute an important aspect of emotion regulation in reappraisal, suggesting that semantic processes may be more important to understand the mechanism of emotion regulation than previously thought. PMID:26217277

Smoking cannabis produces a diverse range of effects, including impairments in learning and memory. These effects are exerted through action on the endocannabinoid system, which suggests involvement of this system in human cognition. Learning and memory deficits are core symptoms of psychiatric and neurological disorders such as schizophrenia and Alzheimer's disease, and may also be related to endocannabinoid dysfunction in these disorders. However, before new research can focus on potential treatments that work by manipulating the endocannabinoid system, it needs to be elucidated how this system is involved in symptoms of psychiatric disorders. Here we review neuroimagingstudies that investigated acute and non-acute effects of cannabis on human learning and memory function, both in adults and in adolescents. Overall, results of these studies show that cannabis use is associated with a pattern of increased activity and a higher level of deactivation in different memory-related areas. This could reflect either increased neural effort ('neurophysiological inefficiency') or a change in strategy to maintain good task performance. However, the interpretation of these findings is significantly hampered by large differences between study populations in cannabis use in terms of frequency, age of onset, and time that subjects were abstinent from cannabis. Future neuroimagingstudies should take these limitations into account, and should focus on the potential of cannabinoid compounds for treatment of cognitive symptoms in psychiatric disorders.

Attention-deficit/hyperactivity disorder (ADHD) is a persistent neuropsychiatric disorder which is associated with impairments on a variety of cognitive measures and abnormalities in structural and functional brain measures. Genetic factors are thought to play an important role in the etiology of ADHD. The NeuroIMAGEstudy is a follow-up of the Dutch part of the International Multicenter ADHD Genetics (IMAGE) project. It is a multi-site prospective cohort study designed to investigate the course of ADHD, its genetic and environmental determinants, its cognitive and neurobiological underpinnings, and its consequences in adolescence and adulthood. From the original 365 ADHD families and 148 control (CON) IMAGE families, consisting of 506 participants with an ADHD diagnosis, 350 unaffected siblings, and 283 healthy controls, 79 % participated in the NeuroIMAGE follow-up study. Combined with newly recruited participants the NeuroIMAGEstudy comprehends an assessment of 1,069 children (751 from ADHD families; 318 from CON families) and 848 parents (582 from ADHD families; 266 from CON families). For most families, data for more than one child (82 %) and both parents (82 %) were available. Collected data include a diagnostic interview, behavioural questionnaires, cognitive measures, structural and functional neuroimaging, and genome-wide genetic information. The NeuroIMAGE dataset allows examining the course of ADHD over adolescence into young adulthood, identifying phenotypic, cognitive, and neural mechanisms associated with the persistence versus remission of ADHD, and studying their genetic and environmental underpinnings. The inclusion of siblings of ADHD probands and controls allows modelling of shared familial influences on the ADHD phenotype.

The psychopharmacology training experiences and attitudes of Canadian counsellors were the focus of our national Internet-based survey. This study was part of a larger investigation on Canadian counsellors' attitudes, practices, and training experiences related to clients on antidepressants. Results of the current study indicate Canadian…

State-of-the-art neuroimaging techniques have accelerated progress in the study and understanding of sleep in humans. Neuroimagingstudies in primary insomnia remain relatively few, considering the important prevalence of this disorder in the general population. This review examines the contribution of functional and structural neuroimaging to our current understanding of primary insomnia. Functional studies during sleep provided support for the hyperarousal theory of insomnia. Functional neuroimaging also revealed abnormalities in cognitive and emotional processing in primary insomnia. Results from structural studies suggest neuroanatomical alterations in primary insomnia, mostly in the hippocampus, anterior cingulate cortex and orbitofrontal cortex. However, these results are not well replicated across studies. A few magnetic resonance spectroscopy studies revealed abnormalities in neurotransmitter concentrations and bioenergetics in primary insomnia. The inconsistencies among neuroimaging findings on insomnia are likely due to clinical heterogeneity, differences in imaging and overall diversity of techniques and designs employed. Larger samples, replication, as well as innovative methodologies are necessary for the progression of this perplexing, yet promising area of research.

In this paper, I analyze risks and limits of the current psychopharmacology and how both are promoting a new social interpretation of health concept. Besides, I show how such interpretation can be detected in four issues related to safety, equality, psychiatrization of human condition, and autonomy. In the conclusions, I defend, first, the obligation of physician to inform patients about the important long-term uncertainties around psychopharmacology. Second, I justify the necessity of promote more prolonged monitoring of patients treated with such kind of drugs. Third, I insist in the relevance of increasing research about drugs ' adverse effects extended over a long time. And forth, I bring up the utility of health concept to avoid the subjective stigmatization of cognitive or affective traits, to prevent potential problems of inequality and coercion, and to keep from mental disorders caused by attempts of getting psychical states supposedly optimized.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that has a strong genetic basis, and is heterogeneous in its etiopathogenesis and clinical presentation. Neuroimagingstudies, in concert with neuropathological and clinical research, have been instrumental in delineating trajectories of development in children with ASD. Structural neuroimaging has revealed ASD to be a disorder with general and regional brain enlargement, especially in the frontotemporal cortices, while functional neuroimagingstudies have highlighted diminished connectivity, especially between frontal-posterior regions. The diverse and specific neuroimaging findings may represent potential neuroendophenotypes, and may offer opportunities to further understand the etiopathogenesis of ASD, predict treatment response and lead to the development of new therapies. PMID:26234701

Functional neuroimaging measures quantitative changes in neurophysiological parameters coupled to neuronal activity during observable behavior. These results have usually been interpreted by assuming that mental causation of behavior arises from the simultaneous actions of distinct psychological mechanisms or modules. However, reproducible localization of these modules in the brain using functional magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging has been elusive other than for sensory systems. In this paper, we show that neuroenergetic studies using PET, calibrated functional magnetic resonance imaging (fMRI), 13C magnetic resonance spectroscopy, and electrical recordings do not support the standard approach, which identifies the location of mental modules from changes in brain activity. Of importance in reaching this conclusion is that changes in neuronal activities underlying the fMRI signal are many times smaller than the high ubiquitous, baseline neuronal activity, or energy in resting, awake humans. Furthermore, the incremental signal depends on the baseline activity contradicting theoretical assumptions about linearity and insertion of mental modules. To avoid these problems, while making use of these valuable results, we propose that neuroimaging should be used to identify observable brain activities that are necessary for a person's observable behavior rather than being used to seek hypothesized mental processes. PMID:25160670

PTSD in children and adolescents differs from the adult disease. Therapeutic approaches involve both psychotherapy and psychopharmacotherapy. Objectives: The current paper aims at reviewing studies on psychopharmacological treatment of childhood and adolescent PTSD. Additionally, developmental frameworks for PTSD diagnosis and research along with…

Apathy remains a common neuropsychiatric disturbance in the Human Immunodeficiency Virus (HIV-1) despite advances in anti-retroviral treatment (ART). The goal of the current review is to recapitulate findings relating apathy to the deleterious biobehavioral effects of HIV-1 in the post-ART era. Available literatures demonstrate that the emergence of apathy with other neurocognitive and neuropsychiatric symptoms may be attributed to neurotoxic effects of viral proliferation, e.g., aggregative effect of Tat and gp120 on apoptosis, transport and other enzymatic reactions amongst dopaminergic neurons and neuroglia. An assortment of neuroimaging modalities converge on the severity of apathy symptoms associated with the propensity of the virus to replicate within frontal-striatal brain circuits that facilitate emotional processing. Burgeoning research into functional brain connectivity also supports the effects of microvascular and neuro-inflammatory injury linked to aging with HIV-1 on the presentation of neuropsychiatric symptoms. Summarizing these findings, we review domains of HIV-associated neurocognitive and neuropsychiatric impairment linked to apathy in HIV. Taken together, these lines of research suggest that loss of affective, cognitive and behavioral inertia is commensurate with the neuropathology of HIV-1.

Brain imaging is a natural intermediate phenotype to understand the link between genetic information and behavior or brain pathologies risk factors. Massive efforts have been made in the last few years to acquire high-dimensional neuroimaging and genetic data on large cohorts of subjects. The statistical analysis of such data is carried out with increasingly sophisticated techniques and represents a great computational challenge. Fortunately, increasing computational power in distributed architectures can be harnessed, if new neuroinformatics infrastructures are designed and training to use these new tools is provided. Combining a MapReduce framework (TomusBLOB) with machine learning algorithms (Scikit-learn library), we design a scalable analysis tool that can deal with non-parametric statistics on high-dimensional data. End-users describe the statistical procedure to perform and can then test the model on their own computers before running the very same code in the cloud at a larger scale. We illustrate the potential of our approach on real data with an experiment showing how the functional signal in subcortical brain regions can be significantly fit with genome-wide genotypes. This experiment demonstrates the scalability and the reliability of our framework in the cloud with a 2 weeks deployment on hundreds of virtual machines. PMID:24782753

Neuroimaging facilitates the assessment of complementary medicines (CMs) by providing a noninvasive insight into their mechanisms of action in the human brain. This is important for identifying the potential treatment options for target disease cohorts with complex pathophysiologies. The aim of this systematic review was to evaluate study characteristics, intervention efficacy, and the structural and functional neuroimaging methods used in research assessing nutritional and herbal medicines for mild cognitive impairment (MCI) and dementia. Six databases were searched for articles reporting on CMs, dementia, and neuroimaging methods. Data were extracted from 21/2,742 eligible full text articles and risk of bias was assessed. Nine studies examined people with Alzheimer's disease, 7 MCI, 4 vascular dementia, and 1 all-cause dementia. Ten studies tested herbal medicines, 8 vitamins and supplements, and 3 nootropics. Ten studies used electroencephalography (EEG), 5 structural magnetic resonance imaging (MRI), 2 functional MRI (fMRI), 3 cerebral blood flow (CBF), 1 single photon emission tomography (SPECT), and 1 positron emission tomography (PET). Four studies had a low risk of bias, with the majority consistently demonstrating inadequate reporting on randomisation, allocation concealment, blinding, and power calculations. A narrative synthesis approach was assumed due to heterogeneity in study methods, interventions, target cohorts, and quality. Eleven key recommendations are suggested to advance future work in this area. PMID:28303161

Neuroimaging facilitates the assessment of complementary medicines (CMs) by providing a noninvasive insight into their mechanisms of action in the human brain. This is important for identifying the potential treatment options for target disease cohorts with complex pathophysiologies. The aim of this systematic review was to evaluate study characteristics, intervention efficacy, and the structural and functional neuroimaging methods used in research assessing nutritional and herbal medicines for mild cognitive impairment (MCI) and dementia. Six databases were searched for articles reporting on CMs, dementia, and neuroimaging methods. Data were extracted from 21/2,742 eligible full text articles and risk of bias was assessed. Nine studies examined people with Alzheimer's disease, 7 MCI, 4 vascular dementia, and 1 all-cause dementia. Ten studies tested herbal medicines, 8 vitamins and supplements, and 3 nootropics. Ten studies used electroencephalography (EEG), 5 structural magnetic resonance imaging (MRI), 2 functional MRI (fMRI), 3 cerebral blood flow (CBF), 1 single photon emission tomography (SPECT), and 1 positron emission tomography (PET). Four studies had a low risk of bias, with the majority consistently demonstrating inadequate reporting on randomisation, allocation concealment, blinding, and power calculations. A narrative synthesis approach was assumed due to heterogeneity in study methods, interventions, target cohorts, and quality. Eleven key recommendations are suggested to advance future work in this area.

Objective: To consider the limited usefulness of expert guidelines for teaching psychopharmacology. Method: Potential problems using expert guidelines for teaching psychopharmacology are reviewed. Results: Expert guidelines are an important contribution to the growth of evidence-based psychiatry. As such, they may also be used to teach…

Focuses on psychopharmacology and prescription privileges for psychologists. Summarizes nine major findings from Task Force on Psychopharmacology in the Schools, created to review literature on prescription privileges for psychologists; identify specific issues attendant to use of psychoactive medications with children; and clarify implications…

Objective: The author examines one aspect of the psychopharmacology curriculum: the psychology of psychopharmacology. Method: Drawing from his experience teaching this subject to trainees at many different levels and from an emerging evidence base suggesting that psychosocial factors in the doctor-patient relationship may be crucial for medication…

Reviews the current literature on psychological and psychopharmacologic treatments for bulimia nervosa in the adolescent population. Describes the two most researched psychological treatments--cognitive behavior therapy and interpersonal therapy--in terms of treatment protocols and outcome research. Reviews psychopharmacologic treatment, including…

The authors reviewed current literature and curriculum resources on psychopharmacology and social work. They argue that baccalaureate and master of social work courses need to routinely include more in-depth knowledge on psychopharmacology and provide a more critical social work-focused approach to this content due to the increasing complexity of…

Neuroscientists are increasingly using advanced neuroimaging methods to elucidate the intergenerational transmission of human brain circuitry. This new line of work promises to shed light on the ontogeny of complex behavioral traits, including psychiatric disorders, and possible mechanisms of transmission. Here we highlight recent intergenerational neuroimagingstudies and provide recommendations for future work.

Functional and structural brain changes associated with the cognitive processing of emotional visual stimuli were assessed in schizophrenic patients after 16 weeks of antipsychotic treatment with ziprasidone. Forty-five adults aged 18 to 40 were recruited: 15 schizophrenia patients (DSM-IV criteria) treated with ziprasidone (mean daily dose = 120 mg), 15 patients treated with other antipsychotics, and 15 healthy controls who did not receive any medication. Functional and structural neuroimaging data were acquired at baseline and 16 weeks after treatment initiation. In each session, participants selected stimuli, taken from standardized sets, based on their emotional valence. After ziprasidone treatment, several prefrontal regions, typically involved in cognitive control (anterior cingulate and ventrolateral prefrontal cortices), were significantly activated in patients in response to positive versus negative stimuli. This effect was greater whenever they had to select negative compared to positive stimuli, indicating an asymmetric effect of cognitive treatment of emotionally laden information. No such changes were observed for patients under other antipsychotics. In addition, there was an increase in the brain volume commonly recruited by healthy controls and patients under ziprasidone, in response to cognitive processing of emotional information. The structural analysis showed no significant changes in the density of gray and white matter in ziprasidone-treated patients compared to patients receiving other antipsychotic treatments. Our results suggest that functional changes in brain activity after ziprasidone medication precede structural and clinical manifestations, as markers that the treatment is efficient in restoring the functionality of prefrontal circuits involved in processing emotionally laden information in schizophrenia.

The implementation of Mental Health Nurse (MHN) prescribing in the UK remains disappointing. A much cited critique of MHNs prescribing is that it would be unsafe, as MHN would not have the appropriate knowledge of pharmacology to practise mental health prescribing. The knowledge of pharmacology of MHNs with the prescribing qualification has not been assessed in the UK. In addition, the views of MHNs with the prescribing qualification who have undertaken a psychopharmacology course have not been explored. The aims of this study are to measure the efficacy of a 10-day advanced training programme on psychopharmacology on the knowledge levels of MHNs with the prescribing qualification; and to explore the positive and negative experiences of individual participants of the training in psychopharmacology and how it supported their prescribing practice. A repeated measures design was used in which participants acted as their own controls. Participants were assessed 10 weeks before the training programme and again on day one of the training programme using a Multiple Choice Questionnaire. In addition, a series of focus groups were conducted to explore the helpful and unhelpful aspects of the course in sustaining the MHNs' prescribing practice. Following the training period there were significant increases in the MHNs' knowledge of psychopharmacology in comparison with the two base line means. Participants when interviewed 18 months after completing the training described the training as a helpful though they described it had not resulted in large increases in prescribing practice, citing systemic barriers to its implementation. Short and focussed training for MHNs who prescribe may increase their knowledge of psychopharmacology. The development of such programmes may well be part of the solution to support MHNs with the prescribing qualification to prescribe, supported by the views of the MHNs who participated in the focus groups. However, further work is required to remove

At present, the Mexican mint Salvia divinorum is an unregulated hallucinogen. This has resulted in various on-line botanical companies advertising and selling S. divinorum as a legal alternative to other regulated plant hallucinogens. It is predictable that its misuse will increase rapidly. The active ingredient in S. divinorum is the neoclerodane diterpene, salvinorin A (1a), which has been shown to be a kappa agonist both in vitro and in vivo. This review will cover the current state of research into the psychopharmacology of S. divinorum.

While there is no cure for autism spectrum disorder, psychopharmacologic agents are often used with behavioral and educational approaches to treat its comorbid symptoms of hyperactivity, irritability, and aggression. Studies suggest that at least 50% of persons with autism spectrum disorder receive psychotropic medications during their life span. This selective review examines recent studies about the use of psychotropic medications in persons with autism spectrum disorder. The aim was to focus on randomized controlled trials conducted from 1990 to 2010 on this topic. A comprehensive literature search was performed using PubMed and Cochrane databases. Out of 105 studies identified for the review, only 24 were randomized controlled trials. Thus, despite the common use of these medications in autism spectrum disorder, more controlled studies are needed to determine their long-term efficacy and safety.

Advances in modern neuroimaging in combination with behavioral genetics have allowed neuroscientists to investigate how genetic and environmental factors shape human brain structure and function. Estimating the heritability of brain structure and function via twin studies has become one of the major approaches in studying the genetics of the brain. In a classical twin study, heritability is estimated by computing genetic and phenotypic variation based on the similarity of monozygotic and dizygotic twins. However, heritability has traditionally been measured for univariate, scalar traits, and it is challenging to assess the heritability of a spatial process, such as a pattern of neural activity. In this work, we develop a statistical method to estimate phenotypic variance and covariance at each location in a spatial process, which in turn can be used to estimate the heritability of a spatial dataset. The method is based on a dimensionally-reduced model of spatial variation in paired images, in which adjusted least squares estimates can be used to estimate the key model parameters. The advantage of the proposed method compared to conventional methods such as voxelwise or mean-ROI approaches is demonstrated in both a simulation study and a real data study assessing genetic influence on patterns of brain activity in the visual and motor cortices in response to a simple visuomotor task.

This review examines recent functional neuroimaging research of resting-state regional connectivity between brain regions in anxiety disorders. Studies compiled in the PubMed- National Center for Biotechnology Information database targeting resting-state functional connectivity in anxiety disorders were reviewed. Diagnoses included posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), social anxiety disorder (SAD), obsessive-compulsive disorder (OCD), panic disorder (PD), and specific phobia (SP). Alterations to network connectivity were demonstrated in PTSD, GAD, SAD, OCD, and PD in several resting-state investigations. Differences from control subjects were primarily observed in the default mode network within PTSD, SAD, and OCD. Alterations within the salience network were observed primarily in PTSD, GAD, and SAD. Alterations in corticostriatal networks were uniquely observed in OCD. Finally, alterations within somatosensory networks were observed in SAD and PD investigations. Resting-state studies involving SPs as a primary diagnosis (with or without comorbidities) were not generated during the literature search. The emerging use of resting-state paradigms may be an effective method for understanding associations between anxiety disorders. Targeted studies of PD and SPs, meta-analyses of the studies conducted to date, and studies of the impact of specific comorbid presentations, are recommended future research directions.

Purpose To describe the application of neuroimaging analysis, compared to neuropsychological tests and video-electroencephalogram, for the evaluation of refractory epilepsy in a reference centre in Cali, Colombia. Methods Between March 2013 and November 2014, 29 patients, 19 men and 10 women, aged 9–65 years and with refractory epilepsy, were assessed by structural and functional magnetic resonance imaging while performing tasks related to language, verbal and non-verbal memory. Also, volumetric evaluation was performed. A 1.5 Tesla magnetic resonance imaging scanner was used in all cases. Results Neuroimaging evaluation identified 13 patients with mesial temporal sclerosis. The remaining patients were classified as: 10 patients with neoplastic masses, two patients with cortical atrophy, two patients with scarring lesions and two patients with non-structural aetiology. Among patients with mesial temporal sclerosis, comparison between techniques for lateralising the epileptogenic foci was made; the κ index between functional magnetic resonance imaging and hippocampi volumetry was κ = 1.00, agreement between neuroimaging and video-electroencephalogram was good (κ = 0.78) and comparison with a neuropsychological test was mild (κ = 0.24). Conclusions Neuroimagingstudies allow the assessment of functional and structural damage related to epileptogenic lesions and foci, and are helpful to select surgical treatment, conduct intraoperative neuronavigation techniques, predict surgical deficits and evaluate patient recovery. PMID:26427897

Metabolic physiology and functional neuroimaging have played important and complementary roles over the past two decades. In particular, investigations of the mechanisms underlying functional neuroimaging signals have produced fundamental new insights into hemodynamic and metabolic regulation. However, controversies were also raised as regards the metabolic pathways (oxidative vs. non-oxidative) for meeting the energy demand and driving the increases in cerebral blood flow (CBF) during brain activation. In a recent study, with the concurrent functional MRI-MRS measurements, we found that task-evoked energy demand was predominately met through oxidative metabolism (approximately 98%), despite a small increase in cerebral metabolic rate of oxygen (12–17%). In addition, the task-induced increases in CBF were most likely mediated by anaerobic glycolysis rather than oxygen demand. These observations and others from functional neuroimaging support the activation-induced neuron-astrocyte interactions portrayed by the astrocyte-neuron lactate shuttle model. The concurrent developments of neuroimaging methods and metabolic physiology will also pave the way for the future investigation of cerebral hemodynamics and metabolism in disease states. PMID:20725632

eventually gets incorporated into formal treatment guidelines, while researchers have little to guide them as to what kind of new knowledge it is most important to provide. Summary Clinical innovation brings out the ambiguities in our current ethical conceptions of research versus clinical care. Yet, historically, clinical innovation has been an important contributor to progress in psychopharmacology. We argue that clinical innovation should not be discouraged, but rather it should occur under certain ethical conditions. "Almost everyone can and should do research...because almost everyone has a unique observational opportunity at some time in his life which he has an obligation to record....If one considers the fundamental operations or methods of research, one immediately realizes that most people do research at some time or another, except that they do not call their activity by that name. There are seven operations....In simple language they are counting, sorting, measuring, comparing, nature-study, guess testing, and reappraisal....Guess testing is of course what most people think of when the word research is mentioned; except that it is bad manners to call a guess a guess. It should be called an hypothesis. Let us make one plea. Guessing becomes merely a game unless it is done in the context of a plan for action. It is a waste of time elaborating untestable hypotheses [1]." John Cade PMID:17996065

Semantic memory refers to knowledge about people, objects, actions, relations, self, and culture acquired through experience. The neural systems that store and retrieve this information have been studied for many years, but a consensus regarding their identity has not been reached. Using strict inclusion criteria, we analyzed 120 functional neuroimagingstudies focusing on semantic processing. Reliable areas of activation in these studies were identified using the activation likelihood estimate (ALE) technique. These activations formed a distinct, left-lateralized network comprised of 7 regions: posterior inferior parietal lobe, middle temporal gyrus, fusiform and parahippocampal gyri, dorsomedial prefrontal cortex, inferior frontal gyrus, ventromedial prefrontal cortex, and posterior cingulate gyrus. Secondary analyses showed specific subregions of this network associated with knowledge of actions, manipulable artifacts, abstract concepts, and concrete concepts. The cortical regions involved in semantic processing can be grouped into 3 broad categories: posterior multimodal and heteromodal association cortex, heteromodal prefrontal cortex, and medial limbic regions. The expansion of these regions in the human relative to the nonhuman primate brain may explain uniquely human capacities to use language productively, plan, solve problems, and create cultural and technological artifacts, all of which depend on the fluid and efficient retrieval and manipulation of semantic knowledge. PMID:19329570

The question of whether creative insight varies across problem types has recently come to the forefront of studies of creative cognition. In the present study, to address the nature of creative insight, the coordinate-based activation likelihood estimation (ALE) technique was utilized to individually conduct three quantitative meta-analyses of neuroimaging experiments that used the compound remote associate (CRA) task, the prototype heuristic (PH) task and the Chinese character chunk decomposition (CCD) task. These tasks were chosen because they are frequently used to uncover the neurocognitive correlates of insight. Our results demonstrated that creative insight reliably activates largely non-overlapping brain regions across task types, with the exception of some shared regions: the CRA task mainly relied on the right parahippocampal gyrus, the superior frontal gyrus and the inferior frontal gyrus; the PH task primarily depended on the right middle occipital gyrus (MOG), the bilateral superior parietal lobule/precuneus, the left inferior parietal lobule, the left lingual gyrus and the left middle frontal gyrus; and the CCD task activated a broad cerebral network consisting of most dorsolateral and medial prefrontal regions, frontoparietal regions and the right MOG. These results provide the first neural evidence of the task dependence of creative insight. The implications of these findings for resolving conflict surrounding the different theories of creative cognition and for defining insight as a set of heterogeneous processes are discussed.

Conscious sensory perception and its modulation by volition are integral to human mental life. Functional neuroimaging techniques provide a direct means of identifying and characterizing in vivo the systems-level patterns of brain activity associated with such mental functions. In a series of positron emission tomography activation experiments, we and our colleagues have examined a range of normal and abnormal auditory states that, when contrasted, provide dissociations relevant to the question of the neural substrates of sensory awareness. These dissociations include sensory awareness in the presence and absence of external sensory stimuli, the transition from sensory unawareness to awareness (or vice versa) in the presence of sensory stimuli, and sensory awareness with and without volition. The auditory states studied include hallucinations, mental imagery, cortical deafness modulated by attention, and hearing modulated by sedation. The results of these studies highlight the distributed nature of the functional neuroanatomy that is sufficient, if not necessary, for sensory awareness. The probable roles of unimodal association (as compared with primary) cortices, heteromodal cortices, limbic/paralimbic regions and subcortical structures (such as the thalamus) are discussed. In addition, interactions between pre- and post-rolandic regions are examined in the context of top-down, volitional modulation of sensory awareness. PMID:9854260

Children and adolescents often use complementary and alternative medicine (CAM) treatments outside their indications, particularly to lose weight. Some of the herbal remedies and dietary supplements that may of relevance for psychopharmacological practice are discussed with respect to CAM treatments.

We present a novel group-wise registration method for cortical correspondence for local cortical thickness analysis in human and non-human primate neuroimagingstudies. The proposed method is based on our earlier template based registration that estimates a continuous, smooth deformation field via sulcal curve-constrained registration employing spherical harmonic decomposition of the deformation field. This pairwise registration though results in a well-known template selection bias, which we aim to overcome here via a group-wise approach. We propose the use of an unbiased ensemble entropy minimization following the use of the pairwise registration as an initialization. An individual deformation field is then iteratively updated onto the unbiased average. For the optimization, we use metrics specific for cortical correspondence though all of these are straightforwardly extendable to the generic setting: The first focused on optimizing the correspondence of automatically extracted sulcal landmarks and the second on that of sulcal depth property maps. We further propose a robust entropy metric and a hierarchical optimization by employing spherical harmonic basis orthogonality. We also provide the detailed methodological description of both our earlier work and the proposed method with a set of experiments on a population of human and non-human primate subjects. In the experiment, we have shown that our method achieves superior results on consistency through quantitative and visual comparisons as compared to the existing methods.

We present a novel group-wise registration method for cortical correspondence for local cortical thickness analysis in human and non-human primate neuroimagingstudies. The proposed method is based on our earlier template based registration that estimates a continuous, smooth deformation field via sulcal curve-constrained registration employing spherical harmonic decomposition of the deformation field. This pairwise registration though results in a well-known template selection bias, which we aim to overcome here via a group-wise approach. We propose the use of an unbiased ensemble entropy minimization following the use of the pairwise registration as an initialization. An individual deformation field is then iteratively updated onto the unbiased average. For the optimization, we use metrics specific for cortical correspondence though all of these are straightforwardly extendable to the generic setting: The first focused on optimizing the correspondence of automatically extracted sulcal landmarks and the second on that of sulcal depth property maps. We further propose a robust entropy metric and a hierarchical optimization by employing spherical harmonic basis orthogonality. We also provide the detailed methodological description of both our earlier work and the proposed method with a set of experiments on a population of human and non-human primate subjects. In the experiment, we have shown that our method achieves superior results on consistency through quantitative and visual comparisons as compared to the existing methods. PMID:26113807

Functional near-infrared spectroscopy (fNIRS) is an emerging functional neuroimaging technology offering a relatively non-invasive, safe, portable, and low-cost method of indirect and direct monitoring of brain activity. Most exciting is its potential to allow more ecologically valid investigations that can translate laboratory work into more realistic everyday settings and clinical environments. Our aim is to acquaint clinicians and researchers with the unique and beneficial characteristics of fNIRS by reviewing its relative merits and limitations vis-à-vis other brain-imaging technologies such as functional magnetic resonance imaging (fMRI). We review cross-validation work between fMRI and fNIRS, and discuss possible reservations about its deployment in clinical research and practice. Finally, because there is no comprehensive review of applications of fNIRS to brain disorders, we also review findings from the few studies utilizing fNIRS to investigate neurocognitive processes associated with neurological (Alzheimer's disease, Parkinson's disease, epilepsy, traumatic brain injury) and psychiatric disorders (schizophrenia, mood disorders, anxiety disorders).

Knowledge of psychopharmacology is essential for a clinical psychologist to practice his/her profession, regardless of whether one desires to become licensed to prescribe psychoactive medications. This commentary reiterates a call made almost 20 years ago for all practitioners to gain and utilize this knowledge. Without psychopharmacology knowledge, one is extremely limited in the ability to interact with medical prescribers and to optimally serve their patients as a valued member of the health care team.

Advances in neuroscience and biotechnology have heightened the urgency of the debate over "cosmetic psychopharmacology," the use of drugs to enhance mood and temperament in the absence of illness. Beyond Therapy: Biotechnology and the Pursuit of Happiness (2003), the report of the President's Council on Bioethics, has criticized the use of cosmetic psychopharmacology. The Council claimed that cosmetic psychopharmacology will necessarily lead to "severing the link between feelings of happiness and our actions and experiences in the world," but it provided no satisfactory arguments to support this claim and ignored the possibility that cosmetic psychopharmacology might actually enhance the link between happiness and experience. The Council's arguments against cosmetic psychopharmacology depend heavily on the mistaken belief that Prozac and similar antidepressants are mood brighteners in healthy subjects. The empirical evidence, however, clearly indicates that these drugs are not forms of cosmetic psychopharmacology, thus negating much of the Council's arguments. The use of pharmaceutical agents to enhance mood or personality in normal individuals should not be rejected a priori. Instead, the effects of each agent on the individual and on society must be weighed using sound ethical reasoning and the best evidence available.

Objective To evaluate the impact of therapeutic oral doses of stimulants on the brains of ADHD subjects as measured by MRI-based neuroimagingstudies (morphometric, functional, spectroscopy). Data Sources We searched PubMed and ScienceDirect through the end of calendar year 2011 using the keywords: 1) “psychostimulants” or “methylphenidate” or “amphetamine”, and 2) “neuroimaging” or “MRI” or “fMRI”, and 3) “ADHD” or “ADD” or “Attention-Deficit/Hyperactivity Disorder” or “Attention Deficit Hyperactivity Disorder”. Study Selection We included only English language articles with new data that were case or placebo-controlled and examined ADHD subjects on and off psychostimulants (as well as 5 relevant review papers). Data Extraction We combined details of study design and medication effects in each imaging modality. Results We found 29 published studies that met our criteria. These included 6 structural MRI, 20 functional MRI studies and 3 spectroscopy studies. Methods varied widely in terms of design, analytic technique, and regions of the brain investigated. Despite heterogeneity in methods, however, results were consistent. With only a few exceptions, the data on the effect of therapeutic oral doses of stimulant medication suggest attenuation of structural and functional alterations found in unmedicated ADHD subjects relative to findings in Controls. Conclusions Despite the inherent limitations and heterogeneity of the extant MRI literature, our review suggests that therapeutic oral doses of stimulants decrease alterations in brain structure and function in subjects with ADHD relative to unmedicated subjects and Controls. These medication-associated brain effects parallel, and may underlie, the well-established clinical benefits. PMID:24107764

Over the past decade, an increasing number of neuroimagingstudies have provided insight into the neurobiological mechanisms of posttraumatic stress disorder (PSTD). In particular, molecular neuroimaging techniques have been employed in examining metabolic and neurochemical processes in PTSD. This article reviews molecular neuroimagingstudies in PTSD and focuses on findings using three imaging modalities including positron emission tomography (PET), single photon emission computed tomography (SPECT), and magnetic resonance spectroscopy (MRS). Although there were some inconsistences in the findings, patients with PTSD showed altered cerebral metabolism and perfusion, receptor bindings, and metabolite profiles in the limbic regions, medial prefrontal cortex, and temporal cortex. Studies that have investigated brain correlates of treatment response are also reviewed. Lastly, the limitations of the molecular neuroimagingstudies and potential future research directions are discussed. PMID:28035179

The phenomenology and underlying pathophysiology of bipolar disorder (BD) are heterogeneous. The identification of putative endophenotypes for BD can aid in the investigation of unique patho-etiological pathways, which may lead to the development of personalised preventative and therapeutic approaches for this multi-faceted disorder. We included original studies involving unaffected first-degree relatives of BD patients (URs) and a healthy control (HC) comparison group with no first-degree family history of mental disorders, investigating: 'cold' and 'hot' cognition and functional and structural neuroimaging. Seventy-seven cross-sectional studies met the inclusion criteria. The present review revealed that URs in comparison with HCs showed: (i) widespread deficits in verbal memory, sustained attention, and executive function; (ii) abnormalities in the reactivity to and regulation of emotional information along with aberrant reward processing, and heightened attentional interference by emotional stimuli; and (iii) less consistency in the findings regarding structural and resting state neuroimaging, and electrophysiological measures.

Proof of efficacy of a psychotropic medicinal product is the key point of clinical psychopharmacology. This especially concerns the licensing of a new compound, but apart from this special case, lots of efficacy questions need to be answered in clinical psychopharmacology, such as, e.g. the question of the efficacy of a combination therapy. The methodology of the scientific proof of efficacy has already had a long tradition and has been developed further in the recent past under different aspects. Especially the double-blind randomised parallel group comparison has been developed as a design of highest methodological standard. However, often designs have their place and justification under certain conditions and in relation to certain questions. Although in the recent past, with the over-emphasis of so-called effectiveness studies, the inherent methodological limitations of these studies have not been addressed properly (Möller in Eur Arch Psychiatry Clin Neurosci 258:257-270, 2008), which in consequence devaluated the scientific merits of the classical double-blind randomised control group study designs in the view of those colleagues, who are not that experienced in study design issues. Therefore, it seems to be timely and necessary to review the principle standards and problems concerning the proof of efficacy in clinical psychopharmacology.

Summary Jealousy sits high atop of a list comprised of the most human emotional experiences, although its nature, rationale, and origin are poorly understood. In the past decade, a series of neurological case reports and neuroimaging findings have been particularly helpful in piecing together jealousy’s puzzle. In order to understand and quantify the neurological factors that might be important in jealousy, we reviewed the current literature in this specific field. We made an electronic search, and examined all literature with at least an English abstract, through Mars 2010. The search identified a total of 20 neurological patients, who experienced jealousy in relation with a neurological disorder; and 22 healthy individuals, who experienced jealousy under experimental neuroimaging settings. Most of the clinical cases of reported jealousy after a stroke had delusional-type jealousy. Right hemispheric stroke was the most frequently reported neurological disorder in these patients, although there was a wide range of more diffuse neurological disorders that may be reported to be associated with different other types of jealousy. This is in line with recent neuroimaging data on false beliefs, moral judgments, and intention [mis]understanding. Together the present findings provide physicians and psychologists with a potential for high impact in understanding the neural mechanisms and treatment of jealousy. By combining findings from case reports and neuroimaging data, the present article allows for a novel and unique perspective, and explores new directions into the neurological jealous mind. PMID:21169919

Previous studies have suggested toxic effects of recreational ecstasy use on the serotonin system of the brain. However, it cannot be excluded that observed differences between users and non-users are the cause rather than the consequence of ecstasy use. As part of the Netherlands XTC Toxicity (NeXT) study, we prospectively assessed sustained…

Fragile X syndrome (FraX) remains the most common inherited cause of intellectual disability and provides a valuable model for studying gene-brain-behavior relationships. Over the past 15 years, structural and functional magnetic resonance imaging studies have emerged with the goal of better understanding the neural pathways contributing to the…

Neuroimagingstudies investigating bilingual processes have produced controversial results in determining similarities versus differences between L1 and L2 neural networks. The current meta-analytic study was conducted to examine what factors play a role in the similarities and differences between L1 and L2 networks with a focus on age of acquisition (AOA) and whether the orthographic transparency of L2 is more or less transparent than that of L1. Using activation likelihood estimation (ALE), we found L2 processing involved more additional regions than L1 for late bilinguals in comparison to early bilinguals, suggesting L2 processing is more demanding in late bilinguals. We also provide direct evidence that AOA of L2 influences L1 processing through the findings that early bilinguals had greater activation in the left fusiform gyrus than late bilinguals during L1 processing even when L1 languages were the same in the two groups, presumably due to greater co-activation of orthography in L1 and L2 in early bilinguals. In addition, we found that the same L2 languages evoked different brain activation patterns depending on whether it was more or less transparent than L1 in orthographic transparency. The bilateral auditory cortex and right precentral gyrus were more involved in shallower-than-L1 L2s, suggesting a "sound-out" strategy for a more regular language by involving the phonological regions and sensorimotor regions to a greater degree. In contrast, the left frontal cortex was more involved in the processing of deeper-than-L1 L2s, presumably due to the increased arbitrariness of mapping between orthography and phonology in L2.

Purpose: This study investigated the network of brain regions involved in overt production of vowels, monosyllables, and bisyllables to test hypotheses derived from the Directions Into Velocities of Articulators (DIVA) model of speech production (Guenther, Ghosh, & Tourville, 2006). The DIVA model predicts left lateralized activity in inferior…

A growing body of literature investigating the neural correlates of emotion word processing has emerged in recent years. Written words have been shown to represent a suitable means to study emotion processing and most importantly to address the distinct and interactive contributions of the two dimensions of emotion: valence and arousal. The aim of…

Previous neuropsychological studies on acquired dyslexia revealed a double dissociation in reading impairments. Patients with phonological dyslexia have selective difficulty in reading pseudo-words, while those with surface dyslexia misread exception words. This double dissociation in reading abilities has often been reported in brain-damaged…

Psychologists studying problem solving have, for over 100 years, been interested in the question of whether there are two different modes of solving problems. One mode--problem solving based on analysis--depends on application of past experience to the problem at hand and proceeds incrementally toward solution. The second mode--problem solving…

Over the course of the past decade, contradictory claims have been made regarding the neural bases of deductive reasoning. Researchers have been puzzled by apparent inconsistencies in the literature. Some have even questioned the effectiveness of the methodology used to study the neural bases of deductive reasoning. However, the idea that…

The present state of knowledge of physiological mechanisms underlying nonepileptiform EEG abnormalities is reviewed to clarify the correlation between EEG and neuroimaging. Focal and widespread slow waves, background abnormalities, and bursts of rhythmic slow activity are discussed. EEG phenomena were correlated with lesion size, location, type (white matter vs. gray matter, high density vs. low density), and mass effect. Clinical and experimental accumulated over the past five decades suggest that polymorphic slow activity is generated in cerebral cortex by layers of pyramidal cells and is probably due to partial deafferentation from subcortical areas. Unilateral background activity changes are probably thalamic dysfunction, and bilateral paroxysmal slow activity is due to abnormal thalamocortical circuits combined with cortical pathology. Paroxysmal discharges indicate the presence of epilepsy with possible brain lesion(s). The EEG is a functional test and provides us complementary information to neuroimagingstudies.

Lesion studies link the prefrontal cortex (PFC) to executive functions. However, the evidence from in vivo investigations in healthy people is mixed, and there are no quantitative estimates of the association strength. To examine the relationship between PFC volume and cortical thickness with executive cognition in healthy adults, we conducted a meta-analysis of studies that assessed executive functions and PFC volume (31 samples,) and PFC thickness (10 samples) in vivo, N=3272 participants. We found that larger PFC volume and greater PFC thickness were associated with better executive performance. Stronger associations between executive functions and PFC volume were linked to greater variance in the sample age but was unrelated to the mean age of a sample. Strength of association between cognitive and neuroanatomical indices depended on the executive task used in the study. PFC volume correlated stronger with Wisconsin Card Sorting Test than with digit backwards span, Trail Making Test and verbal fluency. Significant effect size was observed in lateral and medial but not orbital PFC. The results support the “bigger is better” hypothesis of brain-behavior relation in healthy adults and suggest different neural correlates across the neuropsychological tests used to assess executive functions. PMID:24568942

Because the processing capacity of the visual system is limited, selective attention to one part of the visual field comes at the cost of neglecting other parts. In this paper, we review evidence from single-cell studies in monkeys and functional magnetic resonance imaging (fMRI) studies in humans for neural competition and how competition is biased by attention. We suggest that, at the neural level, an important consequence of attention is to enhance the influence of behaviorally relevant stimuli at the expense of irrelevant ones, providing a mechanism for the filtering of distracting information in cluttered visual scenes. Psychophysical evidence suggests that processing outside the focus of attention is attenuated and may be even eliminated under some conditions. A major exception to the critical role of attention may be in the neural processing of emotion-laden stimuli, which are reported to be processed automatically, namely, without attention. Contrary to this prevailing view, in a recent study we found that all brain regions responding differentially to faces with emotional content, including the amygdala, did so only when sufficient resources were available to process those faces. After reviewing our findings, we discuss their implications, in particular (1) how emotional stimuli can bias competition for processing resources; (2) the source of the biasing signal for emotional stimuli; (3) how visual information reaches the amygdala; and finally (4) the relationship between attention and awareness.

Lesion studies link the prefrontal cortex (PFC) to executive functions. However, the evidence from in vivo investigations in healthy people is mixed, and there are no quantitative estimates of the association strength. To examine the relationship between PFC volume and cortical thickness with executive cognition in healthy adults, we conducted a meta-analysis of studies that assessed executive functions and PFC volume (31 samples,) and PFC thickness (10 samples) in vivo, N=3272 participants. We found that larger PFC volume and greater PFC thickness were associated with better executive performance. Stronger associations between executive functions and PFC volume were linked to greater variance in the sample age but was unrelated to the mean age of a sample. Strength of association between cognitive and neuroanatomical indices depended on the executive task used in the study. PFC volume correlated stronger with Wisconsin Card Sorting Test than with digit backwards span, Trail Making Test and verbal fluency. Significant effect size was observed in lateral and medial but not orbital PFC. The results support the "bigger is better" hypothesis of brain-behavior relation in healthy adults and suggest different neural correlates across the neuropsychological tests used to assess executive functions.

Neuropsychological data about acquired impairments in reading and writing provide a strong basis for the theoretical framework of the dual-route models. The present study explored the functional neuroanatomy of the reading and spelling processing system. We describe the reading and writing performance of patient CF, an Italian native speaker who developed an extremely selective reading and spelling deficit (his spontaneous speech, oral comprehension, repetition and oral picture naming were almost unimpaired) in processing double letters associated with surface dyslexia and dysgraphia, following a tumor in the left temporal lobe. In particular, the majority of CF's errors in spelling were phonologically plausible substitutions, errors concerning letter numerosity of consonants, and syllabic phoneme-to-grapheme conversion (PGC) errors. A similar pattern of impairment also emerged in his reading behavior, with a majority of lexical stress errors (the only possible type of surface reading errors in the Italian language, due the extreme regularity of print-to-sound correspondence). CF's neuropsychological profile was combined with structural neuroimaging data, fiber tracking, and functional maps and compared to that of healthy control participants. We related CF's deficit to a dissociation between impaired ventral/lexical route (as evidenced by a fractional anisotropy - FA decrease along the inferior fronto-occipital fasciculus - IFOF) and relatively preserved dorsal/phonological route (as evidenced by a rather full integrity of the superior longitudinal fasciculus - SLF). In terms of functional processing, the lexical-semantic ventral route network was more activated in controls than in CF, while the network supporting the dorsal route was shared by CF and the control participants. Our results are discussed within the theoretical framework of dual-route models of reading and spelling, emphasize the importance of the IFOF both in lexical reading and spelling, and offer

Alterations to myelin may be a core pathological feature of neurodegenerative diseases. Although white matter microstructural differences have been described in Parkinson's disease (PD), it is unknown whether such differences include alterations of the brain’s myelin content. Thus, the objective of the current study is to measure and compare brain myelin content between PD patients and age-matched controls. In this cross-sectional study, 63 participants from the Longitudinal MRI in Parkinson's Disease study underwent brain MRI, Unified Parkinson's Disease Rating Scale (UPDRS) scoring, and cognitive asessments. Subjects were imaged with the mcDEPSOT (multi-component driven equilibrium single pulse observation of T1 and T2), a multicomponent relaxometry technique that quantifies longitudinal and transverse relaxation rates (R1 and R2, respectively) and the myelin water fraction (VFM), a surrogate for myelin content. A voxel-wise approach was used to compare R1, R2, and VFM measures between PD and control groups, and to evaluate relationships with age as well as disease duration, UPDRS scores, and daily levodopa equivalent dose. PD subjects had higher VFM than controls in frontal and temporal white matter and bilateral thalamus. Greater age was strongly associated with lower VFM in both groups, while an age-by-group interaction suggested a slower rate of VFM decline in the left putamen with aging in PD. Within the PD group, measures of disease severity, including UPDRS, daily levodopa equivalent dose, and disease duration, were observed to be related with myelin content in diffuse brain regions. The age-by-group interaction suggests that either PD or dopaminergic therapies allay observed age-related myelin changes. The relationships between VFM and disease severity measures suggests that VFM may provide a surrogate marker for microstructural changes related to Parkinson’s disease. PMID:27706215

Activation likelihood estimation (ALE) meta-analyses were used to examine the neural correlates of prediction error in reinforcement learning. The findings are interpreted in the light of current computational models of learning and action selection. In this context, particular consideration is given to the comparison of activation patterns from studies using instrumental and Pavlovian conditioning, and where reinforcement involved rewarding or punishing feedback. The striatum was the key brain area encoding for prediction error, with activity encompassing dorsal and ventral regions for instrumental and Pavlovian reinforcement alike, a finding which challenges the functional separation of the striatum into a dorsal 'actor' and a ventral 'critic'. Prediction error activity was further observed in diverse areas of predominantly anterior cerebral cortex including medial prefrontal cortex and anterior cingulate cortex. Distinct patterns of prediction error activity were found for studies using rewarding and aversive reinforcers; reward prediction errors were observed primarily in the striatum while aversive prediction errors were found more widely including insula and habenula.

OBJECTIVE—Functional activation studies of semantic processing in healthy adults have yielded conflicting results. The purpose was to evaluate the relative role of the brain regions implicated in semantic processing with converging evidence from imaging studies of patients with impaired semantic processing. METHODS—Semantic memory was assessed in patients with Alzheimer's disease using two measures, and these performance patterns were related to profiles of reduced cerebral functioning obtained with high resolution single photon emission computed tomography (SPECT). Patients with frontotemporal degeneration were similarly evaluated as a control group. RESULTS—Reduced relative cerebral perfusion was seen in parietal and posterior temporal brain regions of patients with Alzheimer's disease but not patients with frontotemporal degeneration. Impairments on semantically guided category membership decision tasks were also seen in patients with Alzheimer's disease but not those with frontotemporal degeneration. Performance on the semantic measures correlated with relative cerebral perfusion in inferior parietal and superior temporal regions of the left hemisphere only in Alzheimer's disease. Relative perfusion was significantly lower in these regions in patients with Alzheimer's disease with semantic difficulty compared with patients with Alzheimer's disease with relatively preserved semantic processing. CONCLUSION—These findings provide converging evidence to support the contribution of superior temporal and inferior parietal regions of the left hemisphere to semantic processing. PMID:9285450

Several functional imaging experiments have clearly established that the fusiform gyri are preferentially responsive to faces, whereas the parahippocampal/lingual gyri are more responsive to buildings. Other studies have demonstrated that famous faces additionally activate the anterior temporal cortex relative to unfamiliar faces, animals, tools, body parts and maps. One explanation for this apparent specialization for known people could be that famous faces are 'semantically unique items'. In other words, they carry unique semantic associations that are not shared by other perceptually similar category members. If this hypothesis is correct, the anterior temporal cortex should also respond to other semantically unique items, such as famous buildings. In this PET study, we investigated the effect of fame (famous relative to non-famous) on activation elicited by famous and non-famous faces and buildings during a same-different matching task. We found that, when the task was held constant, category-specific activations in the fusiform and parahippocampal/lingual areas were not modulated by fame. In contrast, in the left anterior middle temporal gyrus there was an effect of fame that was common to faces and buildings. These results suggest that the identification of famous faces and buildings involves category-specific perceptual processing in the fusiform and parahippocampal/lingual regions, respectively, and shared analysis of unique semantic attributes in the left anterior temporal cortex.

Neurodegenerative disorders leading to dementia are common diseases that affect many older and some young adults. Neuroimaging methods are important tools for assessing and monitoring pathological brain changes associated with progressive neurodegenerative conditions. In this review, the authors describe key findings from neuroimagingstudies (magnetic resonance imaging and radionucleotide imaging) in neurodegenerative disorders, including Alzheimer’s disease (AD) and prodromal stages, familial and atypical AD syndromes, frontotemporal dementia, amyotrophic lateral sclerosis with and without dementia, Parkinson’s disease with and without dementia, dementia with Lewy bodies, Huntington’s disease, multiple sclerosis, HIV-associated neurocognitive disorder, and prion protein associated diseases (i.e., Creutzfeldt-Jakob disease). The authors focus on neuroimaging findings of in vivo pathology in these disorders, as well as the potential for neuroimaging to provide useful information for differential diagnosis of neurodegenerative disorders. PMID:24234359

Bipolar disorder is associated with subtle neuroanatomical deficits including lateral ventricular enlargement, grey matter deficits incorporating limbic system structures, and distributed white matter pathophysiology. Substantial heterogeneity has been identified by structural neuroimagingstudies to date and differential psychotropic medication use is potentially a substantial contributor to this. This selective review of structural neuroimaging and diffusion tensor imaging studies considers evidence that lithium, mood stabilisers, antipsychotic medication and antidepressant medications are associated with neuroanatomical variation. Most studies are negative and suffer from methodological weaknesses in terms of directly assessing medication effects on neuroanatomy, since they commonly comprise posthoc assessments of medication associations with neuroimaging metrics in small heterogenous patient groups. However the studies which report positive findings tend to form a relatively consistent picture whereby lithium and antiepileptic mood stabiliser use is associated with increased regional grey matter volume, especially in limbic structures. These findings are further supported by the more methodologically robust studies which include large numbers of patients or repeated intra-individual scanning in longitudinal designs. Some similar findings of an apparently ameliorative effect of lithium on white matter microstructure are also emerging. There is less support for an effect of antipsychotic or antidepressant medication on brain structure in bipolar disorder, but these studies are further limited by methodological difficulties. In general the literature to date supports a normalising effect of lithium and mood stabilisers on brain structure in bipolar disorder, which is consistent with the neuroprotective characteristics of these medications identified by preclinical studies. PMID:26412064

Proactive and reactive inhibition are generally intended as mechanisms allowing the withholding or suppression of overt movements. Nonetheless, inhibition could also play a pivotal role during covert actions (i.e., potential motor acts not overtly performed, despite the activation of the motor system), such as Motor Imagery (MI). In a previous EEG study, we analyzed cerebral activities reactively triggered during two cued Go/NoGo tasks, requiring execution or withholding of overt or covert imagined actions, respectively. This study revealed activation of pre-supplementary motor area (pre-SMA) and right inferior frontal gyrus (rIFG), key nodes of the network underpinning reactive inhibition of overt responses in NoGo trials, also during MI enactment, enabling the covert nature of the imagined motor response. Taking into account possible proactive engagement of inhibitory mechanisms by cue signals, for an exhaustive interpretation of these previous findings in the present study we analyzed EEG activities elicited during the preparatory phase of our cued overt and covert Go/NoGo tasks. Our results demonstrate a substantial overlap of cerebral areas activated during proactive recruitment and subsequent reactive implementation of motor inhibition in both overt and covert actions; also, different involvement of pre-SMA and rIFG emerged, in accord with the intended type (covert or overt) of incoming motor responses. During preparation of the overt Go/NoGo task, the cue is encoded in a pragmatic mode, as it primes the possible overt motor response programs in motor and premotor cortex and, through preactivation of a pre-SMA-related decisional mechanism, it triggers a parallel preparation for successful response selection and/or inhibition during the response phase. Conversely, the preparatory strategy for the covert Go/NoGo task is centered on priming of an inhibitory mechanism in rIFG, tuned to the instructed covert modality of motor performance and instantiated during

In this methods article, we present a new implementation of a recently reported FSL-integrated neurofeedback tool, the standalone version of “Functional Real-time Interactive Endogenous Neuromodulation and Decoding” (FRIEND). We will refer to this new implementation as the FRIEND Engine Framework. The framework comprises a client-server cross-platform solution for real time fMRI and fMRI/EEG neurofeedback studies, enabling flexible customization or integration of graphical interfaces, devices, and data processing. This implementation allows a fast setup of novel plug-ins and frontends, which can be shared with the user community at large. The FRIEND Engine Framework is freely distributed for non-commercial, research purposes. PMID:25688193

Prejudice is an enduring and pervasive aspect of human cognition. An emergent trend in modern psychology has focused on understanding how cognition is linked to neural function, leading researchers to investigate the neural correlates of prejudice. Research in this area using racial group memberships has quickly highlighted the amygdala as a neural structure of importance. In this article, we offer a critical review of social neuroscientific studies of the amygdala in race-related prejudice. Rather than the dominant interpretation that amygdala activity reflects a racial or outgroup bias per se, we argue that the observed pattern of sensitivity in this literature is best considered in terms of potential threat. More specifically, we argue that negative culturally-learned associations between black males and potential threat better explain the observed pattern of amygdala activity. Finally, we consider future directions for the field and offer specific experiments and predictions to directly address unanswered questions. PMID:24734016

The International Working Group (IWG) has classified Alzheimer's disease (AD) as two different types, the typical form and the atypical form, but clinicopathological studies of atypical AD are limited. Because atypical AD cases usually present with early-onset dementia, we investigated 12 patients with early-onset AD, including two patients with typical AD and 10 patients with atypical AD. Of these patients, six had the posterior variant, three had the frontal variant and one had the logopenic variant mixed with semantic dementia. We reported MRI, single-photon emission CT and neuropathological findings in six representative cases. We also described a "left temporal variant" of AD presenting with transcortical cortical sensory aphasia, which has not been reported previously and is another subtype of the posterior variant of AD. We found a significant correlation between regional cerebral blood flow and counts of NFTs in the cerebral cortices. An atypical presentation with focal neuropsychological symptoms roughly correlated with the density of NFTs in the cerebral cortex and more directly related to spongiform changes in the superficial layers of these areas. In contrast, the distribution of amyloid depositions was diffuse and did not necessarily correlate with focal neuropsychological symptoms. Braak staging or ABC score is not necessarily appropriate to evaluate atypical AD, and instead, spongiform changes in addition to tau pathology in the association cortices better explain the diversity of atypical AD. Interestingly, another patient with a posterior variant of AD had a novel type of atypical plaque, which we referred to as "lucent plaque". They were recognizable with HE staining in the circumference and dystrophic neurites were abundant with Gallyas-Braak staining. These plaques demonstrated intense immunoreactivity to both tau AT-8 and amyloid β (Aβ), suggesting a peculiar coexistence pattern of amyloid and tau in these plaques. Clinicopathological studies

Given ample evidence for shared cortical structures involved in encoding actions, whether or not subsequently executed, a still unsolved problem is the identification of neural mechanisms of motor inhibition, preventing “covert actions” as motor imagery from being performed, in spite of the activation of the motor system. The principal aims of the present study were the evaluation of: 1) the presence in covert actions as motor imagery of putative motor inhibitory mechanisms; 2) their underlying cerebral sources; 3) their differences or similarities with respect to cerebral networks underpinning the inhibition of overt actions during a Go/NoGo task. For these purposes, we performed a high density EEG study evaluating the cerebral microstates and their related sources elicited during two types of Go/NoGo tasks, requiring the execution or withholding of an overt or a covert imagined action, respectively. Our results show for the first time the engagement during motor imagery of key nodes of a putative inhibitory network (including pre-supplementary motor area and right inferior frontal gyrus) partially overlapping with those activated for the inhibition of an overt action during the overt NoGo condition. At the same time, different patterns of temporal recruitment in these shared neural inhibitory substrates are shown, in accord with the intended overt or covert modality of action performance. The evidence that apparently divergent mechanisms such as controlled inhibition of overt actions and contingent automatic inhibition of covert actions do indeed share partially overlapping neural substrates, further challenges the rigid dichotomy between conscious, explicit, flexible and unconscious, implicit, inflexible forms of motor behavioral control. PMID:26000451

Given ample evidence for shared cortical structures involved in encoding actions, whether or not subsequently executed, a still unsolved problem is the identification of neural mechanisms of motor inhibition, preventing "covert actions" as motor imagery from being performed, in spite of the activation of the motor system. The principal aims of the present study were the evaluation of: 1) the presence in covert actions as motor imagery of putative motor inhibitory mechanisms; 2) their underlying cerebral sources; 3) their differences or similarities with respect to cerebral networks underpinning the inhibition of overt actions during a Go/NoGo task. For these purposes, we performed a high density EEG study evaluating the cerebral microstates and their related sources elicited during two types of Go/NoGo tasks, requiring the execution or withholding of an overt or a covert imagined action, respectively. Our results show for the first time the engagement during motor imagery of key nodes of a putative inhibitory network (including pre-supplementary motor area and right inferior frontal gyrus) partially overlapping with those activated for the inhibition of an overt action during the overt NoGo condition. At the same time, different patterns of temporal recruitment in these shared neural inhibitory substrates are shown, in accord with the intended overt or covert modality of action performance. The evidence that apparently divergent mechanisms such as controlled inhibition of overt actions and contingent automatic inhibition of covert actions do indeed share partially overlapping neural substrates, further challenges the rigid dichotomy between conscious, explicit, flexible and unconscious, implicit, inflexible forms of motor behavioral control.

Anorexia nervosa (AN), obsessive–compulsive disorder (OCD), and obsessive–compulsive personality disorder (OCPD) are often co-morbid; however, the aetiology of such co-morbidity has not been well investigated. This study examined brain activation in women with AN and in healthy control (HC) women during the provocation of symmetry/ordering-related anxiety. During provocation, patients with AN showed more anxiety compared to HCs, which was correlated with the severity of symmetry/ordering symptoms. Activation in the right parietal lobe and right prefrontal cortex (rPFC) in response to provocation was reduced in the AN group compared with the HC group. The reduced right parietal activation observed in the AN group is consistent with parietal lobe involvement in visuospatial cognition and with studies of OCD reporting an association between structural abnormalities in this region and the severity of ‘ordering’ symptoms. Reduced rPFC activation in response to symmetry/ordering provocation has similarities with some, but not all, data collected from patients with AN who were exposed to images of food and bodies. Furthermore, the combination of data from the AN and HC groups showed that rPFC activation during symptom provocation was inversely correlated with the severity of symmetry/ordering symptoms. These data suggest that individuals with AN have a diminished ability to cognitively deal with illness-associated symptoms of provocation. Furthermore, our data also suggest that symptom provocation can progressively overload attempts by the rPFC to exert cognitive control. These findings are discussed in the context of the current neurobiological models of AN. PMID:24844926

The prevalence of obesity is high resulting from chronic imbalances between energy intake and expenditure. On the expenditure side, regular exercise is associated with health benefits, including enhanced brain function. The benefits of exercise are not immediate and require persistence to be realized. Brain regions associated with health-related decisions, such as whether or not to exercise or controlling the impulse to engage in immediately rewarding activities (e.g., sedentary behavior), include reward processing and cognitive control regions. A 9 month aerobic exercise study will be conducted in 180 sedentary adults (n = 90 healthy weight [BMI = 18.5 to 26.0 kg/m(2)]; n = 90 obese [BMI = 29.0 to 41.0 kg/m(2)) to examine the brain processes underlying reward processing and impulse control that may affect adherence in a new exercise regimen. The primary aim is to use functional magnetic resonance imaging (fMRI) to examine reward processing and impulse control among participants that adhere (exercise >80% of sessions) and those that do not adhere to a nine-month exercise intervention with secondary analyses comparing sedentary obese and sedentary healthy weight participants. Our results will provide valuable information characterizing brain activation underlying reward processing and impulse control in sedentary obese and healthy weight individuals. In addition, our results may identify brain activation predictors of adherence and success in the exercise program along with measuring the effects of exercise and improved fitness on brain activation.

In this study, the neural mechanism subserving the ability to understand people's emotional and mental states by observing their body language (facial expression, body posture and mimics) was investigated in healthy volunteers. ERPs were recorded in 30 Italian University students while they evaluated 280 pictures of highly ecological displays of emotional body language that were acted out by 8 male and female Italian actors. Pictures were briefly flashed and preceded by short verbal descriptions (e.g., "What a bore!") that were incongruent half of the time (e.g., a picture of a very attentive and concentrated person shown after the previous example verbal description). ERP data and source reconstruction indicated that the first recognition of incongruent body language occurred 300 ms post-stimulus. swLORETA performed on the N400 identified the strongest generators of this effect in the right rectal gyrus (BA11) of the ventromedial orbitofrontal cortex, the bilateral uncus (limbic system) and the cingulate cortex, the cortical areas devoted to face and body processing (STS, FFA EBA) and the premotor cortex (BA6), which is involved in action understanding. These results indicate that face and body mimics undergo a prioritized processing that is mostly represented in the affective brain and is rapidly compared with verbal information. This process is likely able to regulate social interactions by providing on-line information about the sincerity and trustfulness of others.

Late-life depression (LLD) and amnestic mild cognitive impairment (aMCI) can both denote prodromal Alzheimer's disease. While the two concepts share common clinical features, differential diagnosis between them is crucial. The objective of this pilot study was to explore differences in terms of the hippocampal (HC) and entorhinal cortex (EC) volume reduction between LLD and aMCI patients with (aMCI/D+ group) or without (aMCI group) depressive symptoms. Six LLD, 6 aMCI, and 6 aMCI/D+ participants were assessed using a structural magnetic resonance imaging protocol. Manual segmentation of HC and EC was carried out. The results of volumetric comparisons suggest that the HC was larger in aMCI/D+ and LLD subjects compared to aMCI participants. The left EC mean volume was slightly lower in aMCI/D+ subjects. Power analyses revealed that 36 participants per group would suffice to confirm these findings. Overall, these pilot findings suggest that aMCI can be distinguished from LLD based on cerebral atrophy measures, and that HC and EC atrophy in aMCI varies according to the presence or absence of depressive symptoms. PMID:23277788

The prevalence of obesity is high resulting from chronic imbalances between energy intake and expenditure. On the expenditure side, regular exercise is associated with health benefits, including enhanced brain function. The benefits of exercise are not immediate and require persistence to be realized. Brain regions associated with health-related decisions, such as whether or not to exercise or controlling the impulse to engage in immediately rewarding activities (e.g., sedentary behavior), include reward processing and cognitive control regions. A 9 month aerobic exercise study will be conducted in 180 sedentary adults (n = 90 healthy weight [BMI= 18.5 to 26.0 kg/m2]; n = 90 obese [BMI=29.0 to 41.0 kg/m2) to examine the brain processes underlying reward processing and impulse control that may affect adherence in a new exercise regimen. The primary aim is to use functional magnetic resonance imaging (fMRI) to examine reward processing and impulse control among participants that adhere (exercise >80% of sessions) and those that do not adhere to a nine-month exercise intervention with secondary analyses comparing sedentary obese and sedentary healthy weight participants. Our results will provide valuable information characterizing brain activation underlying reward processing and impulse control in sedentary obese and healthy weight individuals. In addition, our results may identify brain activation predictors of adherence and success in the exercise program along with measuring the effects of exercise and improved fitness on brain activation. PMID:24291150

Using proton magnetic resonance spectroscopy ((1)H-MRS), we measured chemical metabolites in the left amygdala and the bilateral orbito-frontal cortex (OFC) in children with autism spectrum disorders (ASD). The concentrations of N-acetylaspartate (NAA) in these regions of ASD were significantly decreased compared to those in the control group. In the autistic patients, the NAA concentrations in these regions correlated with their social quotient. These findings suggest the presence of neuronal dysfunction in the amygdala and OFC in ASD. Dysfunction in the amygdala and OFC may contribute to the pathogenesis of ASD. We performed a near-infrared spectroscopy (NIRS) study to evaluate the mirror neuron system in children with ASD. The concentrations of oxygenated hemoglobin (oxy-Hb) were measured with frontal probes using a 34-channel NIRS machine while the subjects imitated emotional facial expressions. The increments in the concentration of oxy-Hb in the pars opercularis of the inferior frontal gyrus in autistic subjects were significantly lower than those in the controls. However, the concentrations of oxy-Hb in this area were significantly elevated in autistic subjects after they were trained to imitate emotional facial expressions. The results suggest that mirror neurons could be activated by repeated imitation in children with ASD.

Suicidal behaviors result from a complex interaction between social stressors and individual vulnerability. However, little is known of the specific neural network supporting the sensitivity to social stressors in patients at risk of suicidal acts. Using functional Magnetic Resonance Imaging, we investigated brain processing of social rejection in suicide attempters. Thirty-six euthymic women with a history of depression and suicidal behavior were compared to 41 euthymic women with a history of depression but no suicidal attempt, and 28 healthy controls. The Cyberball Game was used as a validated social exclusion paradigm. Relative to healthy controls, both patient groups reported higher levels of social distress related to the task, without significant differences according to suicidal status. Compared to patients without any history of suicide attempt and healthy controls, suicide attempters showed decreased contrast in the left insula and supramarginal gyrus during the exclusion vs. inclusion condition, after controlling for number of depressive episodes, medication, mood disorder type or social phobia. Our study highlights impaired brain response to social exclusion in euthymic female suicide attempters in regions previously implicated in pain tolerance and social cognition. These findings suggest sustained brain dysfunctions related to social perception in suicide attempters.

Despite increasing interest in pathological and non-pathological dissociation, few researchers have focused on the spiritual experiences involving dissociative states such as mediumship, in which an individual (the medium) claims to be in communication with, or under the control of, the mind of a deceased person. Our preliminary study investigated psychography - in which allegedly "the spirit writes through the medium's hand" - for potential associations with specific alterations in cerebral activity. We examined ten healthy psychographers - five less expert mediums and five with substantial experience, ranging from 15 to 47 years of automatic writing and 2 to 18 psychographies per month - using single photon emission computed tomography to scan activity as subjects were writing, in both dissociative trance and non-trance states. The complexity of the original written content they produced was analyzed for each individual and for the sample as a whole. The experienced psychographers showed lower levels of activity in the left culmen, left hippocampus, left inferior occipital gyrus, left anterior cingulate, right superior temporal gyrus and right precentral gyrus during psychography compared to their normal (non-trance) writing. The average complexity scores for psychographed content were higher than those for control writing, for both the whole sample and for experienced mediums. The fact that subjects produced complex content in a trance dissociative state suggests they were not merely relaxed, and relaxation seems an unlikely explanation for the underactivation of brain areas specifically related to the cognitive processing being carried out. This finding deserves further investigation both in terms of replication and explanatory hypotheses.

Despite increasing interest in pathological and non-pathological dissociation, few researchers have focused on the spiritual experiences involving dissociative states such as mediumship, in which an individual (the medium) claims to be in communication with, or under the control of, the mind of a deceased person. Our preliminary study investigated psychography – in which allegedly “the spirit writes through the medium's hand” – for potential associations with specific alterations in cerebral activity. We examined ten healthy psychographers – five less expert mediums and five with substantial experience, ranging from 15 to 47 years of automatic writing and 2 to 18 psychographies per month – using single photon emission computed tomography to scan activity as subjects were writing, in both dissociative trance and non-trance states. The complexity of the original written content they produced was analyzed for each individual and for the sample as a whole. The experienced psychographers showed lower levels of activity in the left culmen, left hippocampus, left inferior occipital gyrus, left anterior cingulate, right superior temporal gyrus and right precentral gyrus during psychography compared to their normal (non-trance) writing. The average complexity scores for psychographed content were higher than those for control writing, for both the whole sample and for experienced mediums. The fact that subjects produced complex content in a trance dissociative state suggests they were not merely relaxed, and relaxation seems an unlikely explanation for the underactivation of brain areas specifically related to the cognitive processing being carried out. This finding deserves further investigation both in terms of replication and explanatory hypotheses. PMID:23166648

Decision-making is strongly influenced by the counterfactual anticipation of personal regret and relief, through a learning process involving the ventromedial-prefrontal cortex. We previously reported that observing the regretful outcomes of another's choices reactivates the regret-network. Here we extend those findings by investigating whether this resonant mechanism also underpins interactive-learning from others' previous outcomes. In this functional-Magnetic-Resonance-Imaging study 24 subjects either played a gambling task or observed another player's risky/non-risky choices and resulting outcomes, thus experiencing personal or shared regret/relief for risky/non-risky decisions. Subjects' risk-aptitude in subsequent choices was significantly influenced by both their and the other's previous outcomes. This influence reflected in cerebral regions specifically coding the effect of previously experienced regret/relief, as indexed by the difference between factual and counterfactual outcomes in the last trial, when making a new choice. The subgenual cortex and caudate nucleus tracked the outcomes that increased risk-seeking (relief for a risky choice, and regret for a non-risky choice), while activity in the ventromedial-prefrontal cortex, amygdala and periaqueductal gray-matter reflected those reducing risk-seeking (relief for a non-risky choice, and regret for a risky choice). Crucially, a subset of the involved regions was also activated when subjects chose after observing the other player's outcomes, leading to the same behavioural change as in a first person experience. This resonant neural mechanism at choice may subserve interactive-learning in decision-making.

As clinical reasoning is a fundamental competence of physicians for good clinical practices, medical academics have endeavored to teach reasoning skills to undergraduate students. However, our current understanding of student-level clinical reasoning is limited, mainly because of the lack of evaluation tools for this internal cognitive process. This functional magnetic resonance imaging (fMRI) study aimed to examine the clinical reasoning processes of medical students in response to problem-solving questions. We recruited 24 2nd-year medical students who had completed their preclinical curriculum. They answered 40 clinical vignette-based multiple-choice questions during fMRI scanning. We compared the imaging data for 20 problem-solving questions (reasoning task) and 20 recall questions (recall task). Compared to the recall task, the reasoning task resulted in significantly greater activation in nine brain regions, including the dorsolateral prefrontal cortex and inferior parietal cortex, which are known to be associated with executive function and deductive reasoning. During the recall task, significant activation was observed in the brain regions that are related to memory and emotions, including the amygdala and ventromedial prefrontal cortex. Our results support that medical students mainly solve clinical questions with deductive reasoning involving prior knowledge structures and executive functions. The problem-solving questions induced the students to utilize higher cognitive functions compared with the recall questions. Interestingly, the results suggested that the students experienced some emotional distress while they were solving the recall questions. In addition, these results suggest that fMRI is a promising research tool for investigating students' cognitive processes.

Unlike focal or partial epilepsy, which has a confined range of influence, idiopathic generalized epilepsy (IGE) often affects the whole or a larger portion of the brain without obvious, known cause. It is important to understand the underlying network which generates epileptic activity and through which epileptic activity propagates. The aim of the present study was to investigate the thalamocortical relationship using non-invasive imaging modalities in a group of IGE patients. We specifically investigated the roles of the mediodorsal nuclei in the thalami and the medial frontal cortex in generating and spreading IGE activities. We hypothesized that the connectivity between these two structures is key in understanding the generation and propagation of epileptic activity in brains affected by IGE. Using three imaging techniques of EEG, fMRI and EEG-informed fMRI, we identified important players in generation and propagation of generalized spike-and-wave discharges (GSWDs). EEG-informed fMRI suggested multiple regions including the medial frontal area near to the anterior cingulate cortex, mediodorsal nuclei of the thalamus, caudate nucleus among others that related to the GSWDs. The subsequent seed-based fMRI analysis revealed a reciprocal cortical and bi-thalamic functional connection. Through EEG-based Granger Causality analysis using (DTF) and adaptive DTF, within the reciprocal thalamocortical circuitry, thalamus seems to serve as a stronger source in driving cortical activity from initiation to the propagation of a GSWD. Such connectivity change starts before the GSWDs and continues till the end of the slow wave discharge. Thalamus, especially the mediodorsal nuclei, may serve as potential targets for deep brain stimulation to provide more effective treatment options for patients with drug-resistant generalized epilepsy. PMID:26448912

Studying the way athletes predict actions of their peers during fast-ball sports, such as a tennis, has proved to be a valuable tool for increasing our knowledge of intention understanding. The working model in this area is that the anticipatory representations of others' behaviors require internal predictive models of actions formed from pre-established and shared representations between the observer and the actor. This model also predicts that observers would not be able to read accurately the intentions of a competitor if the competitor were to perform the action without prior knowledge of their intention until moments before the action. To test this hypothesis, we recorded brain activity from 25 male tennis players while they performed a novel behavioral tennis intention inference task, which included two conditions: (i) one condition in which they viewed video clips of a tennis athlete who knew in advance where he was about to act/serve (initially intended serves) and (ii) one condition in which they viewed video clips of that same athlete when he did not know where he was to act/serve until the target was specified after he had tossed the ball into the air to complete his serve (non-initially intended serves). Our results demonstrated that (i) tennis expertise is related to the accuracy in predicting where another server intends to serve when that server knows where he intends to serve before (but not after) he tosses the ball in the air; and (ii) accurate predictions are characterized by the recruitment of both cortical areas within the human mirror neuron system (that is known to be involved in higher-order (top-down) processes of embodied cognition and shared representation) and subcortical areas within brain regions involved in procedural memory (caudate nucleus). Interestingly, inaccurate predictions instead recruit areas known to be involved in low-level (bottom-up) computational processes associated with the sense of agency and self-other distinction

Objective To investigate the neural substrate of premenstrual dysphoric disorder (PMDD), the authors used [15O]H2O positron emission tomography (PET) regional cerebral blood flow (rCBF) and blood-oxygen-level-dependent (BOLD) functional MRI (fMRI) signal measurements during working memory in conjunction with a 6-month hormone manipulation protocol. Method PET and fMRI scans were obtained from women with prospectively confirmed PMDD and asymptomatic comparison subjects while they completed the n-back task during three hormone conditions: ovarian suppression induced by the gonadotropin-releasing hormone agonist leuprolide acetate, leuprolide plus estradiol, and leuprolide plus progesterone. Fifteen patients and 15 matched comparison subjects underwent PET imaging. Fourteen patients and 14 comparison subjects underwent fMRI. For each hormone condition, rCBF was measured with [15O]H2O PET, and BOLD signal was measured with fMRI, both during an n-back working memory paradigm. Global Assessment of Functioning Scale (GAF) scores and clinical characteristics were obtained for each patient before hormone manipulation, and symptoms were measured before and during the protocol. Results In both the PET and fMRI studies, a main effect of diagnosis was observed, with PMDD patients showing greater prefrontal activation than comparison subjects. In the patient group, the degree to which dorsolateral prefrontal cortex activation was abnormally increased correlated with several dimensions of disease: disability as indicated by GAF scores, age at symptom onset, duration of PMDD, and differences in pre- and postmenses PMDD symptoms. Conclusions Abnormal working memory activation in PMDD, specifically in the dorsolateral prefrontal cortex, is related to PMDD severity, symptoms, age at onset, and disease burden. These results support the clinical relevance of the findings and the proposal that dorsolateral prefrontal cortex dysfunction represents a substrate of risk for PMDD. The

Structure and function are closely related in the healthy human brain. In patients with chronic heroin exposure, brain imaging studies have identified long-lasting changes in gray matter (GM) volume. More recently, we showed that acute application of heroin in dependent patients results in hypoperfusion of fronto-temporal areas compared with the placebo condition. However, the relationship between structural and cerebral blood flow (CBF) changes in heroin addiction has not yet been investigated. Moreover, it is not known whether there is any interaction between the chronic structural changes and the short and long-term effects on perfusion caused by heroin. Using a double-blind, within-subject design, heroin or placebo (saline) was administered to 14 heroin-dependent patients from a stable heroin-assisted treatment program, in order to observe acute short-term effects. Arterial spin labeling (ASL) was used to calculate perfusion quantification maps in both treatment conditions, while Voxel-Based Morphometry (VBM) was conducted to calculate regional GM density. VBM and ASL data were used to calculate homologous correlation fields by Biological Parametric Mapping (BPM) and a whole-brain Pearson r correlation. We correlated each perfusion condition (heroin and placebo) separately with a VBM sample that was identical for the two treatment conditions. It was assumed that heroin-associated perfusion is manifested in short-term effects, while placebo-associated perfusion is more related to long-term effects. In order to restrict our analyses to fronto-temporal regions, we used an explicit mask for our analyses. Correlation analyses revealed a significant positive correlation in frontal areas between GM and both perfusion conditions (heroin and placebo). Heroin-associated perfusion was also negatively correlated with GM in the inferior temporal gyrus on both hemispheres. These findings indicate that, in heroin-dependent patients, low GM volume is positively associated with

OBJECTIVES To assess cognitive impairment and depression in aging former professional football (National Football League [NFL]) players and to identify neuroimaging correlates of these dysfunctions. DESIGN We compared former NFL players with cognitive impairment and depression, cognitively normal retired players who were not depressed, and matched healthy control subjects. SETTING Research center in the North Texas region of the United States. PATIENTS Cross-sectional sample of former NFL players with and without a history of concussion recruited from the North Texas region and age-, education-, and IQ-matched controls. Thirty-four retired NFL players (mean age, 61.8 years) underwent neurological and neuropsychological assessment. A subset of 26 players also underwent detailed neuroimaging; imaging data in this subset were compared with imaging data acquired in 26 healthy matched controls. MAIN OUTCOME MEASURES Neuropsychological measures, clinical diagnoses of depression, neuroimaging mea-sures of white matter pathology, and a measure of cerebral blood flow. RESULTS Of the 34 former NFL players, 20 were cognitively normal. Four were diagnosed as having a fixed cognitive deficit; 8, mild cognitive impairment; 2, dementia; and 8, depression. Of the subgroup in whom neuroimaging data were acquired, cognitively impaired participants showed the greatest deficits on tests of naming, word finding, and visual/verbal episodic memory. We found significant differences in white matter abnormalities in cognitively impaired and depressed retired players compared with their respective controls. Regional blood flow differences in the cognitively impaired group (left temporal pole, inferior parietal lobule, and superior temporal gyrus) corresponded to regions associated with impaired neurocognitive performance (problems with memory, naming, and word finding). CONCLUSIONS Cognitive deficits and depression appear to be more common in aging former NFL players compared with healthy

Psychopharmacology is a powerful tool in psychiatry; however, it is one that demands responsibility in order to deal with the ethical complexities that accompany advances in the field. It is important that questions are asked and that ethical mindfulness and sensitivity are developed along with clinical skills. In order to cultivate and deepen ethical awareness and subsequently solve issues in optimal fashion, investment should be made in the development of an ethical decision-making process as well as in education in the ethics of psychopharmacology to trainees in the field at all stages of their educational development. A clear approach to identifying ethical problems, engaging various ethical concepts in considering solutions and then applying these principles in problem resolution is demanded. An openness in identifying and exploring issues has become crucial to the future development and maturation of psychopharmacologists, both research and clinical. Consideration must be given to the social implications of psychopharmacological practice, with the best interests of patients always paramount. From both a research and clinical perspective, psychopharmacology has to be practised with fairness, sensitivity and ethical relevance to all. While ethical issues related to psychopharmacological practice are varied and plentiful, this review focuses on advances in technology and biological sciences, personal integrity, special populations, and education and training.

Background: Subjective tinnitus is a frequent, impairing condition, which may also cause neurotransmitter imbalance at the cochlea. Psychopharmacologic agents, although not being the first-line treatment for tinnitus, may modulate cochlear neurotransmission, thereby influencing the subjective tinnitus experience. Method: A comprehensive review of MEDLINE literature (from January 1990–January 2010) was performed searching for: “tinnitus”, major classes of psychopharmacological agents, and psychiatric disorders. The most relevant clinical evidence is reported briefly along with a concise description of the main neurotransmitters purported to be involved in tinnitus, in order to provide the reader with a rational evaluation of tinnitus therapy with psychopharmacological agents. Results: Although strong methodological issues limit the reliability of the current results, a broad number of psychopharmacological agents have already been considered for tinnitus, both as candidate triggers or potential therapies. Conclusions: Selected psychopharmacological drugs may play a role in the clinical management of this disorder. While the rational use of these agents for the treatment of tinnitus should not be overlooked, research should be undertaken on their neuromodulating actions at the cochlea. PMID:20628627

There are clear limitations to the currently approved pharmacotherapies of depression, including the fact that they are all essentially monoamine-based, have modest efficacy and a relatively slow onset of efficacy, and suffer from significant tolerability issues, particularly in the long term, including sexual dysfunction, weight gain, and cognitive impairments. This article reviews some of the most promising novel mechanisms that are not represented in compounds currently approved for depression in either the United States or Europe and that may represent the future of the psychopharmacologic treatment of depression, potentially addressing some of the efficacy and tolerability issues of antidepressants on the market. These potential antidepressant treatments include the multimodal serotonergic agents, the triple uptake inhibitors, the neurokinin-based novel therapies, the glutamatergic treatments, the nicotinic receptor-based treatments, the neurogenesis-based treatments, and antiglucocorticoid therapies. Some of these mechanisms appear to be more advanced in terms of drug development than others, but they all contribute to the global effort to develop more effective and better tolerated treatments for major depressive disorder.

The maturation of in vivo neuroimaging has led to incredible quantities of digital information about the human brain. While much is made of the data deluge in science, neuroimaging represents the leading edge of this onslaught of "big data". A range of neuroimaging databasing approaches has streamlined the transmission, storage, and dissemination of data from such brain imaging studies. Yet few, if any, common solutions exist to support the science of neuroimaging. In this article, we discuss how modern neuroimaging research represents a multifactorial and broad ranging data challenge, involving the growing size of the data being acquired; sociological and logistical sharing issues; infrastructural challenges for multi-site, multi-datatype archiving; and the means by which to explore and mine these data. As neuroimaging advances further, e.g. aging, genetics, and age-related disease, new vision is needed to manage and process this information while marshalling of these resources into novel results. Thus, "big data" can become "big" brain science.

The author focuses on neuroradiology with emphasis on the current imaging modalities. There are chapters on angiography, myelography, nuclear medicine, ultrasonography, computer tomography (CT), and magnetic resonance (MR) imaging. The other chapters are dedicated to the spine, skull, head and neck, and pediatric neuroimaging.

Seven topics previously described in this column are revisited. The use of quantitative electroencephalography has been shown in a prospective study to be effective for predicting antidepressant treatment response. A novel antidepressant drug, agomelatine, has generated much controversy, and its development for the U.S. market was discontinued. A long awaited revised system for categorizing the safety of medications during pregnancy and lactation has finally been published by the Food and Drug Administration. Dextromethorphan/quinidine, eslicarbazepine acetate, levomilnacipran, and esketamine are recent examples of drugs that were developed based on the complex concepts of chirality and stereochemistry. Lisdexamfetamine, a stimulant drug, failed to show benefit as an augmentation therapy for the treatment of depression. The combination drug naltrexone/bupropion was finally approved as a therapy for obesity, after its cardiovascular safety was confirmed in a prospective premarketing study. Further development of the glucocorticoid receptor antagonist drug mifepristone as a treatment for psychotic depression was stopped based on a large negative trial, but the drug continues to be investigated for other potential psychiatric indications. These examples illustrate how the field of psychopharmacology continues to evolve.

Tinnitus is the perception of phantom sound in the absence of a corresponding external source. It is a highly prevalent disorder, and most cases are caused by cochlear injury that leads to peripheral deafferentation, which results in adaptive changes in the CNS. In this article we critically assess the recent neuroimagingstudies in individuals with tinnitus that suggest that the disorder is accompanied by functional and structural brain abnormalities in distributed auditory and non-auditory brain regions. Moreover, we consider how the identification of the neuronal mechanisms underlying the different forms of tinnitus would benefit from larger studies, replication and comprehensive clinical assessment of patients.

Nosological classification in psychiatry, as it is currently applied, does not facilitate biological and psychopharmacological research. • Syndromal acuity has disappeared. Consequently, it is impossible to determine: (i) vi/hether a particular drug affects a particular symptom configuration; (ii) what exactly the behavioral correlate of a particular biological disturbance is. The problem of unfocused diagnoses is greatly magnified by the phenomenon called comorbidity. • The boundary between distress and disorder is illdefined. • Symptom configuration and certain nonsymptomatological variables such as duration and severity are prematurely linked, so as to conceptualize categorical entities. The validity of those constructs has not been sufficiently demonstrated. This undermines the validity of biological studies and leads to “nosologomania,” ie, an ever-growing series of undervalidated psychiatric “disorders.” • Symptoms are grouped horizontally as if they all had the same diagnostic “valence.” This, however, is highly unlikely. • The nosological disease model is unconditionally and uncritically accepted. Alternative models are ignored, particularly the reaction-form model, though it has substantial heuristic value, and deserves to be thoroughly scrutinized. (Research) strategies to remedy this situation are pointed out. PMID:22034250

Quantitative, qualitative, and innovative application of bibliometric research performance indicators to anatomy and radiology research and education can enhance cross-fertilization between the two disciplines. We aim to use these indicators to identify long-term trends in dissemination of publications in neuroimaging anatomy (including both productivity and citation rates), which has subjectively waned in prestige during recent years. We examined publications over the last 40 years in two neuroradiological journals, AJNR and Neuroradiology, and selected and categorized all neuroimaging anatomy research articles according to theme and type. We studied trends in their citation activity over time, and mathematically analyzed these trends for 1977, 1987, and 1997 publications. We created a novel metric, "citation half-life at 10 years postpublication" (CHL-10), and used this to examine trends in the skew of citation numbers for anatomy articles each year. We identified 367 anatomy articles amongst a total of 18,110 in these journals: 74.2% were original articles, with study of normal anatomy being the commonest theme (46.7%). We recorded a mean of 18.03 citations for each anatomy article, 35% higher than for general neuroradiology articles. Graphs summarizing the rise (upslope) in citation rates after publication revealed similar trends spanning two decades. CHL-10 trends demonstrated that more recently published anatomy articles were likely to take longer to reach peak citation rate. Bibliometric analysis suggests that anatomical research in neuroradiology is not languishing. This novel analytical approach can be applied to other aspects of neuroimaging research, and within other subspecialties in radiology and anatomy, and also to foster anatomical education.

With the dissemination of non-invasive human neuroimaging techniques such as fMRI and the advancement of cognitive science, neuroimagingstudies focusing on emotions and social cognition have become established. Along with this advancement, behavioral economics taking emotional and social factors into account for economic decisions has been merged with neuroscientific studies, and this interdisciplinary approach is called neuroeconomics. Past neuroeconomics studies have demonstrated that subcortical emotion-related brain structures play an important role in "irrational" decision-making. The research field that investigates the role of central neurotransmitters in this process is worthy of further development. Here, we provide an overview of recent molecular neuroimagingstudies to further the understanding of the neurochemical basis of "irrational" or emotional decision-making and the future direction, including clinical implications, of the field.

The detrimental effects of prenatal alcohol exposure on the developing brain include structural brain anomalies as well as cognitive and behavioral deficits. Initial neuroimagingstudies of fetal alcohol spectrum disorders (FASD) using magnetic resonance imaging (MRI) confirmed previous autopsy reports of overall reduction in brain volume and central nervous system (CNS) disorganization, with specific structural abnormalities of the corpus callosum, cerebellum, caudate, and hippocampus. Advances in neuroimaging techniques have allowed detection of regional increases in cortical thickness and gray matter volume along with decreased volume and disorganization of white matter in individuals with FASD. In addition, functional imaging studies have found functional and neurochemical differences in those prenatally exposed to alcohol. Behavioral alterations noted in individuals with FASD are consistent with the findings noted in the brain imaging studies. Continued neuroimagingstudies are needed to further advance understanding of the neuroteratogenic effects of alcohol. PMID:19731391

Psychopharmacological treatments have been used with increased frequency to treat a variety of internalizing and externalizing disorders in children. Given the potential impact that medication has on children's school performance, school psychologists should be involved in helping physicians and families make effective decisions by assisting with…

This article reviews several approaches used to teach psychopharmacology for graduate clinical psychology students. In order to promote engagement and increase student interest, students were broken up into groups and were asked to demonstrate their understanding of the material through a variety of interactive games (i.e., game-based learning, or…

In the last decade, the use of medication to treat psychological disorders has greatly expanded. In order to work effectively in school and community settings, counselors will need a sophisticated knowledge of psychopharmacology. This article describes the curriculum, structure, resources, and teaching methods suggested for effective instruction…

Objective: The authors summarize two special sessions focused on the teaching of psychopharmacology at the 2003 and 2004 annual meeting of the American College of Neuropsychopharmacology (ACNP). The focus was on whether "improving the teaching-learning process" in psychiatric residency programs could improve clinical practice. Method: Problems of…

Certain mental disorders are caused by or accompanied by neurochemical abnormalities. The use of psychotropic medications has dramatically increased over the past two decades in all age groups, particularly with children. Therefore, psychopharmacology, the branch of pharmacology dealing with the psychological effects of drugs, needs to be…

Discusses issues regarding the use of a pharmacological approach to the treatment of children with serious emotional and mental disorders that interfere with learning. Addresses the current state of psychopharmacological treatment for diagnostic entities and behavioral symptomatology. Discusses the roles of the child, family, and health and…

The use of functional neuroimaging techniques has advanced what is known about the neural mechanisms used to support language processing in aphasia resulting from brain damage. This paper highlights recent findings derived from neuroimagingstudies focused on neuroplasticity of language networks, the role of the left and right hemispheres in this process, and studies examining how treatment affects the neurobiology of recovery. We point out variability across studies as well as factors related to this variability, and we emphasize challenges that remain for research. PMID:18957184

Neuroimagingstudies of Turner syndrome can advance our understanding of the X chromosome in brain development, and the modulatory influence of endocrine factors. There is increasing evidence from neuroimagingstudies that TX individuals have significant differences in the anatomy, function, and metabolism of a number of brain regions; including…

Dopamine replacement therapy in the form of levodopa results in a significant proportion of patients with Parkinson's disease developing debilitating dyskinesia. This significantly complicates further treatment and negatively impacts patient quality of life. A greater understanding of the neurobiological mechanisms underlying levodopa-induced dyskinesia (LID) is therefore crucial to develop new treatments to prevent or mitigate LID. Such investigations in humans are largely confined to assessment of neurochemical and cerebrovascular blood flow changes using positron emission tomography and functional magnetic resonance imaging. However, recent evidence suggests that LID is associated with specific morphological changes in the frontal cortex and midbrain, detectable by structural MRI and voxel-based morphometry. Current human neuroimaging methods however lack sufficient resolution to reveal the biological mechanism driving these morphological changes at the cellular level. In contrast, there is a wealth of literature from well-established rodent models of LID documenting detailed post-mortem cellular and molecular measurements. The combination therefore of advanced neuroimaging methods and rodent LID models offers an exciting opportunity to bridge these currently disparate areas of research. To highlight this opportunity, in this mini-review, we provide an overview of the current clinical evidence for morphological changes in the brain associated with LID and identify potential cellular mechanisms as suggested from human and animal studies. We then suggest a framework for combining small animal MRI imaging with rodent models of LID, which may provide important mechanistic insights into the neurobiology of LID.

We developed a structure-property-activity relationship (SPAR)-model for psychopharmacological drugs acting as non-competitive 5-HT(3A) receptor antagonists by using a decision-tree learner provided by the RapidMiner machine learning tool. A single molecular descriptor, namely the molecular dipole moment per molecular weight (mu/MW), predicts whether or not a substance non-competitively antagonizes 5-HT-induced Na(+) currents. A low mu/MW is compatible with drug-cumulation in apolar lipid rafts. This study confirms that size-intensive descriptors allow the development of compact SPAR models.

Neuroimaging, particularly that based upon functional magnetic resonance (fMRI), has become a dominant tool in cognitive neuroscience. This review provides a personal and selective perspective on its past, present, and future. Two trends currently characterize the field that broadly reflect a pursuit of “where”- and “how”-type questions. The latter addresses basic mechanisms related to the expression of task-induced neural activity and is likely to be an increasingly important theme in the future. This trend entails an enhanced symbiosis among investigators pursuing similar questions in fields such as computational and theoretical neuroscience as well as through the detailed analysis of microcircuitry. PMID:18995825

For accurate reading comprehension, readers must first learn to map letters to their corresponding speech sounds and meaning and then they must string the meanings of many words together to form a representation of the text. Furthermore, readers must master the complexities involved in parsing the relevant syntactic and pragmatic information necessary for accurate interpretation. Failure in this process can occur at multiple levels and cognitive neuroscience has been helpful in identifying the underlying causes of success and failure in reading single words and in reading comprehension. In general, neurobiological studies of skilled reading comprehension indicate a highly overlapping language circuit for single word reading, reading comprehension and listening comprehension with largely quantitative differences in a number of reading and language related areas. This paper reviews relevant research from studies employing neuroimaging techniques to study reading with a focus on the relationship between reading skill, single word reading, and text comprehension. PMID:23662034

Background When we observe an individual performing a motor act (e.g. grasping a cup) we get two types of information on the basis of how the motor act is done and the context: what the agent is doing (i.e. grasping) and the intention underlying it (i.e. grasping for drinking). Here we examined the temporal dynamics of the brain activations that follow the observation of a motor act and underlie the observer's capacity to understand what the agent is doing and why. Methodology/Principal Findings Volunteers were presented with two-frame video-clips. The first frame (T0) showed an object with or without context; the second frame (T1) showed a hand interacting with the object. The volunteers were instructed to understand the intention of the observed actions while their brain activity was recorded with a high-density 128-channel EEG system. Visual event-related potentials (VEPs) were recorded time-locked with the frame showing the hand-object interaction (T1). The data were analyzed by using electrical neuroimaging, which combines a cluster analysis performed on the group-averaged VEPs with the localization of the cortical sources that give rise to different spatio-temporal states of the global electrical field. Electrical neuroimaging results revealed four major steps: 1) bilateral posterior cortical activations; 2) a strong activation of the left posterior temporal and inferior parietal cortices with almost a complete disappearance of activations in the right hemisphere; 3) a significant increase of the activations of the right temporo-parietal region with simultaneously co-active left hemispheric sources, and 4) a significant global decrease of cortical activity accompanied by the appearance of activation of the orbito-frontal cortex. Conclusions/Significance We conclude that the early striking left hemisphere involvement is due to the activation of a lateralized action-observation/action execution network. The activation of this lateralized network mediates the

Object-location memory (OLM) enables us to keep track of the locations of objects in our environment. The neurocognitive model of OLM (Postma, A., Kessels, R. P. C., & Van Asselen, M. (2004). The neuropsychology of object-location memory. In G. L. Allen (Ed.), Human spatial memory: Remembering where (pp. 143-160). Mahwah, NJ: Lawrence Erlbaum, Postma, A., Kessels, R. P. C., & Van Asselen, M. (2008). How the brain remembers and forgets where things are: The neurocognition of object-location memory. Neuroscience & Biobehavioral Reviews, 32, 1339-1345. doi: 10.1016/j.neubiorev.2008.05.001 ) proposes that distinct brain regions are specialised for different subprocesses of OLM (object processing, location processing, and object-location binding; categorical and coordinate OLM; egocentric and allocentric OLM). It was based mainly on findings from lesion studies. However, recent episodic memory studies point to a contribution of additional or different brain regions to object and location processing within episodic OLM. To evaluate and update the neurocognitive model of OLM, we therefore conducted a systematic literature search for lesion as well as functional neuroimagingstudies contrasting small-space episodic OLM with object memory or location memory. We identified 10 relevant lesion studies and 8 relevant functional neuroimagingstudies. We could confirm some of the proposals of the neurocognitive model of OLM, but also differing hypotheses from episodic memory research, about which brain regions are involved in the different subprocesses of small-space episodic OLM. In addition, we were able to identify new brain regions as well as important research gaps.

Recent research suggests that neuroplastic and neuroinflammatory changes may account for the mode of action of electroconvulsive therapy (ECT), although extant data do not allow for a clear disambiguation between these two hypotheses. Multimodal neuroimaging approaches (for example, combining structural and metabolic information) may help in clarifying this issue. Here we aimed to assess longitudinal changes in (i) regional gray matter (GM) volumes and (ii) hippocampal metabolite concentrations throughout an acute course of bitemporal ECT, as well as (iii) to determine the association between imaging changes and clinical improvement. We assessed 12 patients with treatment-resistant depression (TRD) at four time points (pre-treatment, after the first ECT session, after the ninth ECT session and 15 days after ECT course completion) and 10 healthy participants at two time points, 5 weeks apart. Patients with TRD showed bilateral medial temporal lobe (MTL) and perigenual anterior cingulate cortex volume increases. Left MTL volume increase was associated with (i) a hippocampal N-acetylaspartate concentration decrease, (ii) a hippocampal Glutamate+Glutamine concentration increase and (iii) significant clinical improvement. The observed findings are, in part, compatible with both neuroplastic and neuroinflammatory changes induced by ECT. We postulate that such phenomena may be interrelated, therefore reconciling the neuroplasticity and neuroinflammatory hypotheses of ECT action.

In this paper, it was reviewed neuroimaging results of the pituitary gland in psychiatric disorders, particularly schizophrenia, mood disorders, anxiety disorders, and somatoform disorders. The author made internet search in detail by using PubMed database including the period between 1980 and 2012 October. It was included in the articles in English, Turkish and French languages on pituitary gland in psychiatric disorders through structural or functional neuroimaging results. After searching mentioned in the Methods section in detail, investigations were obtained on pituitary gland neuroimaging in a variety of psychiatric disorders. There have been so limited investigations on pituitary neuroimaging in psychiatric disorders including major psychiatric illnesses like schizophrenia and mood disorders. Current findings are so far from the generalizability of the results. For this reason, it is required to perform much more neuroimagingstudies of pituitary gland in all psychiatric disorders to reach the diagnostic importance of measuring it.

Somatic treatments other than psychotropic drugs are increasingly used in the patients with obsessive compulsive disorder (OCD), however there has been little systematic review of them. Therefore, the present review deals with a variety of somatic treatment methods excluding psychotropic drugs. A literature search was performed on the PubMed database from the beginning of 1980, to September 2012, for published English, Turkish and French-language articles of somatic treatment approaches (excluding psychopharmacological agents) in the treatment of OCD. The search was carried out by using some terms in detail. Afterwards, the obtained investigations on electroconvusive therapy (ECT), deep brain stimulation (DBS), neurosurgical methods and transcranial magnetic stimulation (TMS) were presented. Although psychopharmacological treatment and psychotherapeutic approaches are primary treatment modalities in the management of OCD, other somatic treatment options seem to be used as alternatives, especially for patients with treatmentresistant OCD.

Psychopharmacology has revolutionized psychiatric practice but raises a number of ethical issues. This review from an American perspective first describes ethics analyses and attempts to portray the ethical practitioner. Pressures that interfere with appropriate prescribing come from outside the prescriber and from within, including from insurers, other treatment staff and the prescriber's own will to act for the patient. Clinicians also face binds in which alternate choices seem to have merit and leave the prescriber feeling pulled in contradictory directions, frequently related to risk-benefit dilemmas. The ethics of psychopharmacology poses many questions that cannot yet be answered at the current state of the field. Pharmacology also seems to promote extremes of attitudes, such as "All such drugs are poisons" and the like. This review then provides some risk management principles, and concludes that such a review, though not comprehensive, may serve to open questions that are not always considered by clinicians.

Rates of prescriptions for very young children have increased notably in the last 20 years. These changes have occurred in the context of increasing attention to early childhood mental health, availability of medications perceived to be safer than older medications, application of the medical model to the mental health care of young children, as well as other cultural shifts. Psychopharmacological treatment for any patient, but especially very young children, requires consideration of central nervous system (CNS) and metabolic development and issues of diagnostic validity and should be guided by an empirical literature. In young children, this literature is quite limited. In this article, the authors review developmental issues involved in psychopharmacological treatment and present existing literature and practical guidelines for common preschool diagnoses, recognizing that for some disorders, the extant literature does not support even consideration of medications.

Rationale Nonmedical use and abuse of prescription opioids is a significant problem in the USA. Little attention has been paid to assessing the relative psychopharmacological profile (including abuse liability-related effects) of specific prescription opioids. Objectives The aim of this study is to directly compare the psychopharmacological profile of two oral opioids within the same subject. Methods A randomized, placebo-controlled, crossover study was done in which 20 non-drug-abusing volunteers ingested 10 and 20 mg of oxycodone, 30 and 60 mg of morphine, and placebo in separate sessions. Drug doses were equated on an objective measure of opiate effects: miosis. Subjective, psychomotor, reinforcing, and physiological effects of the opioids were assessed. Results In general, the two opioids at equimiotic doses produced similar prototypic opiate-like effects and psychomotor impairment of similar magnitude. However, several effects were found only with 20 mg oxycodone. Both drugs produced abuse liability-related subjective effects but also dysphoric effects, particularly with 60 mg morphine. Neither drug at either dose functioned as a reinforcer, as measured by the Multiple Choice Procedure. Relative potency ratios indicated an average oxycodone:morphine ratio of 1:3. Conclusions The psychopharmacological profile of oxycodone and morphine at equimiotic doses had many similarities; however, differences were found in producing abuse liability-related and dysphoric effects. In the medical community, it is commonly accepted that oral oxycodone is 1.5 to 2 times as potent as oral morphine in producing analgesia; using this ratio, although patients may experience similar degrees of pain relief, those receiving oxycodone may be experiencing stronger and potentially different psychopharmacological effects. PMID:17899018

Provenance, the description of the history of a set of data, has grown more important with the proliferation of research consortia-related efforts in neuroimaging. Knowledge about the origin and history of an image is crucial for establishing data and results quality; detailed information about how it was processed, including the specific software routines and operating systems that were used, is necessary for proper interpretation, high fidelity replication and re-use. We have drafted a mechanism for describing provenance in a simple and easy to use environment, alleviating the burden of documentation from the user while still providing a rich description of an image’s provenance. This combination of ease of use and highly descriptive metadata should greatly facilitate the collection of provenance and subsequent sharing of data. PMID:18519166

The metabolic effects of stress are known to have significant health effects in both humans and animals. Most of these effects are mediated by the major stress hormonal axis in the body, the hypothalamic-pituitary-adrenal (HPA) axis. Within the central nervous system (CNS), the hippocampus, the amygdala and the prefrontal cortex as part of the limbic system are believed to play important roles in the regulation of the HPA axis. With the advent of structural and functional neuroimaging techniques, the role of different CNS structures in the regulation of the HPA axis can be investigated more directly. In the current paper, we summarize the findings obtained in our laboratory in the context of stress and HPA axis regulation. Our laboratory has developed and contributed to the development of manual and automated segmentation protocols from structural magnetic resonance imaging (MRI) scans for assessment of hippocampus, amygdala, medial temporal lobe and frontal lobe structures. Employing these protocols, we could show significant age-related changes in HC volumes, which were different between men and women, with pre-menopausal women showing smaller age-related volume decline compared to men. We could recently extent these findings by showing how estrogen therapy after menopause leads to higher volumes in the HC. Investigating possible neurotoxicity effects of steroids, we showed effects of long-term steroid exposure on HC volumes, and investigated variability of HC volumes in relation to HPA axis regulation in young and elderly populations. Here, we were able to follow-up from non-imaging studies showing that subjects low in self-esteem have higher cortisol stress responses, and the HC emerged as the critical link between these variables. Recently, we have made two more important discoveries with regard to HC volume: we could show that HC volume is as variable in young as it is in older adults, in subjects ranging in age from 18 to 80 years. Also, we have linked birth

It has been suggested that impulsive behavior is caused by dysfunctional serotonergic 5-HT neurotransmission in the central nervous system (CNS). Brain neuroimagingstudies have shown that behavioral inhibition is linked to the activation of cortex sites such as the ventral frontal cortex. Positron emission tomography (PET) imaging with [(18)F]altanserin to characterize 5-HT(2A) receptor binding revealed a reduction in 5-HT(2A) binding in the ventral frontal cortex in women who had recovered from impulsive diseases. These clinical, neuroimaging, and pharmacological studies appear to support the hypothesis that functional alteration of neurotransmission due to genetic polymorphisms of the 5-HT receptors may be involved in impulsive behavior modulation. Following evaluation by a self-reporting measure, it was proposed that a polymorphism in the promoter of the 5-HT(2A) receptor gene is the underlying cause of impulsive behavior; however, this hypothesis is not convincing. We examined whether the polymorphism in the 5-HT(2A) receptor gene promoter is involved in impulsive aggression by evaluating a behavioral task (Go/No-go task) in normal volunteers. The polymorphism of the 5-HT(2A) receptor gene promoter in lymphocytes from 71 volunteers was analyzed by using PCR. Impulsivity was defined as the number of commission errors (responding when one should not) recorded during a Go/No-go task; a larger number of commission errors indicate greater difficulty in inhibiting impulsive behavior. The subjects of the A-1438A allele group for the 5-HT(2A) receptor gene made more commission errors under the punishment-reward (PR)condition in a Go/No-go task than those in the G-1438G group. In the present review, we discuss and suggest the possible involvement of the A-1438A polymorphism of the 5HT2A receptor gene promoter in impulsive behavior. This hypothesis was evaluated by using a behavioral task measure that could directly reveal impulsive behavioral traits in humans.

Neuroscientists have long sought to study the dynamic activity of the human brain-what's happening in the brain, that is, while people are thinking, feeling, and acting. Ideally, an inside look at brain function would simultaneously and continuously measure the biochemical state of every cell in the central nervous system. While such a miraculous method is science fiction, a century of progress in neuroimaging technologies has made such simultaneous and continuous measurement a plausible fiction. Despite this progress, practitioners of modern neuroimaging struggle with two kinds of limitations: those that attend the particular neuroimaging methods we have today and those that would limit any method of imaging neural activity, no matter how powerful. In this essay, I consider the liabilities and potential of techniques that measure human brain activity. I am concerned here only with methods that measure relevant physiologic states of the central nervous system and relate those measures to particular mental states. I will consider in particular the preeminent method of functional neuroimaging: BOLD fMRI. While there are several practical limits on the biological information that current technologies can measure, these limits-as important as they are-are minor in comparison to the fundamental logical restraints on the conclusions that can be drawn from brain imaging studies.

Background Obsessive–compulsive disorder (OCD) is characterized by maladaptive repetitive behaviors that persist despite feedback. Using multimodal neuroimaging, we tested the hypothesis that this behavioral rigidity reflects impaired use of behavioral outcomes (here, errors) to adaptively adjust responses. We measured both neural responses to errors and adjustments in the subsequent trial to determine whether abnormalities correlate with symptom severity. Since error processing depends on communication between the anterior and the posterior cingulate cortex, we also examined the integrity of the cingulum bundle with diffusion tensor imaging. Methods Participants performed the same antisaccade task during functional MRI and electroencephalography sessions. We measured error-related activation of the anterior cingulate cortex (ACC) and the error-related negativity (ERN). We also examined post-error adjustments, indexed by changes in activation of the default network in trials surrounding errors. Results OCD patients showed intact error-related ACC activation and ERN, but abnormal adjustments in the post- vs. pre-error trial. Relative to controls, who responded to errors by deactivating the default network, OCD patients showed increased default network activation including in the rostral ACC (rACC). Greater rACC activation in the post-error trial correlated with more severe compulsions. Patients also showed increased fractional anisotropy (FA) in the white matter underlying rACC. Conclusions Impaired use of behavioral outcomes to adaptively adjust neural responses may contribute to symptoms in OCD. The rACC locus of abnormal adjustment and relations with symptoms suggests difficulty suppressing emotional responses to aversive, unexpected events (e.g., errors). Increased structural connectivity of this paralimbic default network region may contribute to this impairment. PMID:25057466

Understanding how the nature of interference might influence the recruitments of the neural systems is considered as the key to understanding cognitive control. Although, interference processing in the emotional domain has recently attracted great interest, the question of whether there are separable neural patterns for emotional and non-emotional interference processing remains open. Here, we performed an activation likelihood estimation meta-analysis of 78 neuroimaging experiments, and examined common and distinct neural systems for emotional and non-emotional interference processing. We examined brain activation in three domains of interference processing: emotional verbal interference in the face-word conflict task, non-emotional verbal interference in the color-word Stroop task, and non-emotional spatial interference in the Simon, SRC and Flanker tasks. Our results show that the dorsal anterior cingulate cortex (ACC) was recruited for both emotional and non-emotional interference. In addition, the right anterior insula, presupplementary motor area (pre-SMA), and right inferior frontal gyrus (IFG) were activated by interference processing across both emotional and non-emotional domains. In light of these results, we propose that the anterior insular cortex may serve to integrate information from different dimensions and work together with the dorsal ACC to detect and monitor conflicts, whereas pre-SMA and right IFG may be recruited to inhibit inappropriate responses. In contrast, the dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex (PPC) showed different degrees of activation and distinct lateralization patterns for different processing domains, which suggests that these regions may implement cognitive control based on the specific task requirements. PMID:27895564

Accurate and robust brain extraction is a critical step in most neuroimaging analysis pipelines. In particular, for the large-scale multi-site neuroimagingstudies involving a significant number of subjects with diverse age and diagnostic groups, accurate and robust extraction of the brain automatically and consistently is highly desirable. In this paper, we introduce population-specific probability maps to guide the brain extraction of diverse subject groups, including both healthy and diseased adult human populations, both developing and aging human populations, as well as non-human primates. Specifically, the proposed method combines an atlas-based approach, for coarse skull-stripping, with a deformable-surface-based approach that is guided by local intensity information and population-specific prior information learned from a set of real brain images for more localized refinement. Comprehensive quantitative evaluations were performed on the diverse large-scale populations of ADNI dataset with over 800 subjects (55 ∼ 90 years of age, multi-site, various diagnosis groups), OASIS dataset with over 400 subjects (18 ∼ 96 years of age, wide age range, various diagnosis groups), and NIH pediatrics dataset with 150 subjects (5 ∼ 18 years of age, multi-site, wide age range as a complementary age group to the adult dataset). The results demonstrate that our method consistently yields the best overall results across almost the entire human life span, with only a single set of parameters. To demonstrate its capability to work on non-human primates, the proposed method is further evaluated using a rhesus macaque dataset with 20 subjects. Quantitative comparisons with popularly used state-of-the-art methods, including BET, Two-pass BET, BET-B, BSE, HWA, ROBEX and AFNI, demonstrate that the proposed method performs favorably with superior performance on all testing datasets, indicating its robustness and effectiveness.

The patient who sustains a traumatic brain injury (TBI) typically undergoes neuroimagingstudies, usually in the form of computed tomography (CT) and magnetic resonance imaging (MRI). In most cases the neuroimaging findings are clinically assessed with descriptive statements that provide qualitative information about the presence/absence of visually identifiable abnormalities; though little if any of the potential information in a scan is analyzed in any quantitative manner, except in research settings. Fortunately, major advances have been made, especially during the last decade, in regards to image quantification techniques, especially those that involve automated image analysis methods. This review argues that a systems biology approach to understanding quantitative neuroimaging findings in TBI provides an appropriate framework for better utilizing the information derived from quantitative neuroimaging and its relation with neuropsychological outcome. Different image analysis methods are reviewed in an attempt to integrate quantitative neuroimaging methods with neuropsychological outcome measures and to illustrate how different neuroimaging techniques tap different aspects of TBI-related neuropathology. Likewise, how different neuropathologies may relate to neuropsychological outcome is explored by examining how damage influences brain connectivity and neural networks. Emphasis is placed on the dynamic changes that occur following TBI and how best to capture those pathologies via different neuroimaging methods. However, traditional clinical neuropsychological techniques are not well suited for interpretation based on contemporary and advanced neuroimaging methods and network analyses. Significant improvements need to be made in the cognitive and behavioral assessment of the brain injured individual to better interface with advances in neuroimaging-based network analyses. By viewing both neuroimaging and neuropsychological processes within a systems biology

While brain imaging in the clinical setting is largely a practice of looking at images, research neuroimaging is a quantitative and integrative enterprise. Images are run through complex batteries of processing and analysis routines to generate numeric measures of brain characteristics. Other measures potentially related to brain function - demographics, genetics, behavioral tests, neuropsychological tests - are key components of most research studies. The canonical scanner - PACS - viewing station axis used in clinical practice is therefore inadequate for supporting neuroimaging research. Here, we model the neuroimaging research enterprise as a workflow. The principal components of the workflow include data acquisition, data archiving, data processing and analysis, and data utilization. We also describe a set of open-source applications to support each step of the workflow and the transitions between these steps. These applications include DIGITAL IMAGING AND COMMUNICATIONS IN MEDICINE viewing and storage tools, the EXTENSIBLE NEUROIMAGING ARCHIVE TOOLKIT data archiving and exploration platform, and an engine for running processing/analysis pipelines. The overall picture presented is aimed to motivate open-source developers to identify key integration and communication points for interoperating with complimentary applications.

On the publication of Robert Lowell's Life Studies in 1959, some critics were shocked by the poet's use of seemingly frank autobiographical material, in particular the portrayal of his hospitalizations for bipolar disorder. During the late fifties and throughout the sixties, a rich vein, influenced by Lowell, developed in American poetry. Also during this time, the nascent science of psychopharmacology competed with and complemented the more established somatic treatments, such as psychosurgery, shock treatments, and psychoanalytical therapies. The development of Thorazine was a remarkable breakthrough allowing patients previously thought incurable to leave hospital. In 1955, the release of Miltown, the first 'minor' tranquilizer, was heralded with a media fanfare promising a new dawn of psychological cure-all. These two events blurred the boundary between 'normality' and madness by making treatment in the community more widely possible and by medicalizing more commonplace distress. Lowell's early depictions of madness situate it as emblematic of the cultural malaise of 'the tranquilized fifties.' By his final collection, Day by Day (1977), mental illness had lost its symbolic power. These late poems explore the power of art as a way of representing and remedying suffering in a culture where psychopharmacology has normalized madness.

CS is an autosomal recessive multisystem disorder, which is mainly characterized by neurologic and sensory impairment, cachectic dwarfism, and photosensitivity. We describe the neuroimaging features (MR imaging, ¹H-MR spectroscopy, and CT) in the various clinical subtypes of CS from a cohort of genetically and biochemically proved cases. Hypomyelination, calcifications, and brain atrophy were the main imaging features. Calcifications were typically found in the putamen and less often in the cortex and dentate nuclei. Severe progressive atrophy was seen in the supratentorial white matter, the cerebellum, the corpus callosum, and the brain stem. Patients with early-onset disease displayed more severe hypomyelination and prominent calcifications in the sulcal depth of the cerebral cortex, but atrophy was less severe in late-onset patients. On proton MR spectroscopy, lactate was detected and Cho and NAA values were decreased. These combined neuroradiologic findings can help in the differential diagnosis of CS, distinguishing it from other leukoencephalopathies and/or cerebral calcifications in childhood.

A national sample of 320 school-based, practicing members of the National Association of School Psychologists provided information on (a) their caseloads receiving medications, (b) types of school psychopharmacology training opportunities available and perceptions of their current training in child psychopharmacology, and (c) information about…

OBJECTIVE: To report the assessment of psychopharmacology on the certification and recertification exams in general psychiatry and in the subspecialties administered by the American Board of Psychiatry and Neurology (ABPN). METHODS: The ABPN's core competencies for psychiatrists were reviewed. The number of items addressing psychopharmacology or…

Attention deficit hyperactivity disorder (ADHD) is a common condition with a high societal burden. The present guidelines summarise current literature, generating expert consensus recommendations for the treatment of ADHD in children and adults. These guidelines also provide a review of recent research in the fields of neuroimaging, neuropsychology and genetics of ADHD. Novel discoveries in these areas have informed physiological models for the disease. Since the publication of the previous British Association for Psychopharmacology guidelines in 2008, new drugs have been licensed and further compounds are being investigated. The publication of randomised controlled trials of psychological interventions has contributed to the range of treatment options for ADHD. As the disorder has been diagnosed more frequently there has been greater focus on comorbid conditions and how they impact treatment. Services have continued to develop for the treatment of ADHD in adults and care agreements have been introduced to facilitate access to treatment.

The integration of longitudinal brain structure analysis with neurointensive care strategies continues to be a substantial difficulty facing the traumatic brain injury (TBI) research community. For patient-tailored case analysis, it remains challenging to establish how lesion profile modulates longitudinal changes in cortical structure and connectivity, as well as how these changes lead to behavioral, cognitive and neural dysfunction. Additionally, despite the clinical potential of morphometric and connectomic studies, few analytic tools are available for their study in TBI. Here we review the state of the art in structural and connectomic neuroimaging for the study of TBI and illustrate a set of recently-developed, patient-tailored approaches for the study of TBI-related brain atrophy and alterations in morphometry as well as inter-regional connectivity. The ability of such techniques to quantify how injury modulates longitudinal changes in cortical shape, structure and circuitry is highlighted. Quantitative approaches such as these can be used to assess and monitor the clinical condition and evolution of TBI victims, and can have substantial translational impact, especially when used in conjunction with measures of neuropsychological function. PMID:24844173

The integration of longitudinal brain structure analysis with neurointensive care strategies continues to be a substantial difficulty facing the traumatic brain injury (TBI) research community. For patient-tailored case analysis, it remains challenging to establish how lesion profile modulates longitudinal changes in cortical structure and connectivity, as well as how these changes lead to behavioral, cognitive and neural dysfunction. Additionally, despite the clinical potential of morphometric and connectomic studies, few analytic tools are available for their study in TBI. Here we review the state of the art in structural and connectomic neuroimaging for the study of TBI and illustrate a set of recently-developed, patient-tailored approaches for the study of TBI-related brain atrophy and alterations in morphometry as well as inter-regional connectivity. The ability of such techniques to quantify how injury modulates longitudinal changes in cortical shape, structure and circuitry is highlighted. Quantitative approaches such as these can be used to assess and monitor the clinical condition and evolution of TBI victims, and can have substantial translational impact, especially when used in conjunction with measures of neuropsychological function.

The purpose of this article is to discuss the use of music (i.e., two original songs, "Neurotransmitter Twitter" and "Parkinson's Shuffle") to teach aspects of psychopharmacology to students in the course Psychiatric/Mental Health Nursing. Songs were incorporated in both the clinical and classroom settings. This innovative teaching method allowed students the opportunity to revisit the information through multiple exposures of the content for reinforcement and enhancement of student learning in a fun, creative approach. Brain-based research will be discussed, along with the process of development.

Psychopharmacology has become a major approach to treatment in primary medical care. However, combined psychiatric and medical illness can give rise to some challenging diagnostic problems. Furthermore, drug treatment of patients with such illnesses can involve important drug-disease interactions and drug-drug interactions. One should keep in mind the issues that arise when an emotionally troubled patient would benefit from a psychotropic drug but a concurrent medical illness complicates this treatment. An awareness of both the medical and psychiatric issues involved may make successful treatment possible. PMID:7269559

Nonspecific factors have long been known in both psychotherapy and psychopharmacology. In recent years, 2 studies showed that placebo benefits were lower when the treated subjects were told that the placebo, presented as an active treatment, cost less. One of these studies had assessed motor and other outcomes in Parkinson disease patients; the other had assessed analgesia in paid, healthy volunteers to whom electric shocks were administered. The implication of the finding that lower treatment cost may diminish treatment gains is that patients who receive generic medicines may have lower expectations and may consequently derive less placebo-related benefit. This could be of concern in psychiatric disorders that are characterized by a large placebo response. Although the 2 "placebo cost" studies cannot be easily generalized to clinical and especially psychiatric contexts, clinicans should consider offering reassurance to patients receiving generic drugs that cost, per se, has no bearing on treatment-related benefit.

Recent epidemiological and experimental studies suggest a link between cognitive decline in late adulthood and sports concussions sustained in early adulthood. In order to provide the first in vivo neuroanatomical evidence of this relation, the present study probes the neuroimaging profile of former athletes with concussions in relation to cognition. Former athletes who sustained their last sports concussion >3 decades prior to testing were compared with those with no history of traumatic brain injury. Participants underwent quantitative neuroimaging (optimized voxel-based morphometry [VBM], hippocampal volume, and cortical thickness), proton magnetic resonance spectroscopy ((1)H MRS; medial temporal lobes and prefrontal cortices), and neuropsychological testing, and they were genotyped for APOE polymorphisms. Relative to controls, former athletes with concussions exhibited: 1) Abnormal enlargement of the lateral ventricles, 2) cortical thinning in regions more vulnerable to the aging process, 3) various neurometabolic anomalies found across regions of interest, 4) episodic memory and verbal fluency decline. The cognitive deficits correlated with neuroimaging findings in concussed participants. This study unveiled brain anomalies in otherwise healthy former athletes with concussions and associated those manifestations to the long-term detrimental effects of sports concussion on cognitive function. Findings from this study highlight patterns of decline often associated with abnormal aging.

Background It is unclear to what extent the traditional distinction between neurological and psychiatric disorders reflects biological differences. Aims To examine neuroimaging evidence for the distinction between neurological and psychiatric disorders. Method We performed an activation likelihood estimation meta-analysis on voxel-based morphometry studies reporting decreased grey matter in 14 neurological and 10 psychiatric disorders, and compared the regional and network-level alterations for these two classes of disease. In addition, we estimated neuroanatomical heterogeneity within and between the two classes. Results Basal ganglia, insula, sensorimotor and temporal cortex showed greater impairment in neurological disorders; whereas cingulate, medial frontal, superior frontal and occipital cortex showed greater impairment in psychiatric disorders. The two classes of disorders affected distinct functional networks. Similarity within classes was higher than between classes; furthermore, similarity within class was higher for neurological than psychiatric disorders. Conclusions From a neuroimaging perspective, neurological and psychiatric disorders represent two distinct classes of disorders. PMID:26045351

The roles of the right and left anterior temporal lobes (ATLs) in conceptual knowledge are a source of debate between 4 conflicting accounts. Possible ATL specializations include: (1) Processing of verbal versus non-verbal inputs; (2) the involvement of word retrieval; and (3) the social content of the stimuli. Conversely, the "hub-and-spoke" account holds that both ATLs form a bilateral functionally unified system. Using activation likelihood estimation (ALE) to compare the probability of left and right ATL activation, we analyzed 97 functional neuroimagingstudies of conceptual knowledge, organized according to the predictions of the three specialized hypotheses. The primary result was that ATL activation was predominately bilateral and highly overlapping for all stimulus types. Secondary to this bilateral representation, there were subtle gradations both between and within the ATLs. Activations were more likely to be left lateralized when the input was a written word or when word retrieval was required. These data are best accommodated by a graded version of the hub-and-spoke account, whereby representation of conceptual knowledge is supported through bilateral yet graded connectivity between the ATLs and various modality-specific sensory, motor, and limbic cortices.

Fluorine-18 labeled 2-fluoro-8-hydroxyquinoline ([18F]CABS13) is a promising positron emission tomography (PET) radiopharmaceutical based on a metal chelator developed to probe the “metal hypothesis of Alzheimer’s disease”. Herein, a practical radiosynthesis of [18F]CABS13 was achieved by radiofluorination followed by deprotection of an O-benzyloxymethyl group. Automated production and formulation of [18F]CABS13 resulted in 19 ± 5% uncorrected radiochemical yield, relative to starting [18F]fluoride, with ≥95% chemical and radiochemical purities, and high specific activity (>2.5 Ci/μmol) within 80 minutes. Temporal PET neuroimagingstudies were carried out in female transgenic B6C3- Tg(APPswe,PSEN1dE9)85Dbo/J (APP/PS1) and age-matched wild-type (WT) B6C3F1/J control mice at 3, 7 and 10 months of age. [18F]CABS13 showed an overall higher uptake and retention of radioactivity in the central nervous system of APP/PS1 mice versus WT mice with increasing age. However, PET/magnetic resonance imaging in normal non-human primates revealed that the tracer had low uptake in the brain and rapid formation of a hydrophilic radiometabolite. Identification of more metabolically stable 18F-hydroxyquinolines that can be readily accessed by the radiochemical strategy presented herein is underway. PMID:25776827

The roles of the right and left anterior temporal lobes (ATLs) in conceptual knowledge are a source of debate between 4 conflicting accounts. Possible ATL specializations include: (1) Processing of verbal versus non-verbal inputs; (2) the involvement of word retrieval; and (3) the social content of the stimuli. Conversely, the “hub-and-spoke” account holds that both ATLs form a bilateral functionally unified system. Using activation likelihood estimation (ALE) to compare the probability of left and right ATL activation, we analyzed 97 functional neuroimagingstudies of conceptual knowledge, organized according to the predictions of the three specialized hypotheses. The primary result was that ATL activation was predominately bilateral and highly overlapping for all stimulus types. Secondary to this bilateral representation, there were subtle gradations both between and within the ATLs. Activations were more likely to be left lateralized when the input was a written word or when word retrieval was required. These data are best accommodated by a graded version of the hub-and-spoke account, whereby representation of conceptual knowledge is supported through bilateral yet graded connectivity between the ATLs and various modality-specific sensory, motor, and limbic cortices. PMID:25771223

Functional near-infrared (fNIR) spectroscopy is a wearable neuroimaging device that enables the continuous, non-invasive, and portable monitoring of changes in blood oxygen and blood volume related to human brain function. Over the last three years, studies in the laboratory and under field conditions have established the positive correlation between a participant's performance and oxygenation responses as a function of task load. Our findings indicate that fNIR can effectively monitor attention and working memory in real-life situations. These experimental outcomes compare favorably with functional magnetic resonance imaging (fMRI) studies, and in particular, with the blood oxygenation level dependent (BOLD) signal. The capacity to monitor brain hemodynamics with a wearable device holds promise for the use of fNIR in the creation of a symbiotic relationship between the user and his/her everyday environment. Moreover, under operational conditions, the fNIR system is amenable to integration with other established physiological and neurobehavioral measures, including EEG, eye tracking, pupil reflex, heart rate variability, respiration and electrodermal activity.

In the context of the limitations of structural imaging, brain perfusion and metabolism using SPECT and PET have provided relevant information for the study of cognitive decline. The introduction of the radiotracers for cerebral amyloid imaging has changed the diagnostic strategy regarding Alzheimer's disease, which is currently considered to be a "continuum." According to this new paradigm, the increasing amyloid load would be associated to the preclinical phase and mild cognitive impairment. It has been possible to observe "in vivo" images using 11C-PIB and PET scans. The characteristics of the 11C-PIB image include specific high brain cortical area retention in the positive cases with typical distribution pattern and no retention in the negative cases. This, in combination with 18F-FDG PET, is the basis of molecular neuroimaging as a biomarker. At present, its prognostic value is being evaluated in longitudinal studies. 11C-PIB-PET has become the reference radiotracer to evaluate the presence of cerebral amyloid. However, its availability is limited due to the need for a nearby cyclotron. Therefore, 18F labeled radiotracers are being introduced. Our experience in the last two years with 11C-PIB, first in the research phase and then as being clinically applied, has shown the utility of the technique in the clinical field, either alone or in combination with FDG. Thus, amyloid image is a useful tool for the differential diagnosis of dementia and it is a potentially useful method for early diagnosis and evaluation of future treatments.

Neuroimaging techniques are increasingly used to characterize the neural circuitry mediating actions of inflammation on mood, motivation, and cognition and its relationship to common mental illnesses, particularly major depressive disorder (MDD). In addition, imaging techniques such as single photon emission tomography (SPECT), positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) can index effects of inflammation on specific neurotransmitters, monoamine transporters, metabolites and even activation of discrete cells such as microglia. The special named series 'Neuroimaging, inflammation and behavior' illustrates the power of neuroimaging techniques to characterize discrete actions of inflammation on the brain at neurochemical, cellular, regional and network levels. Combined with careful cognitive assessment and pre-clinical studies, diverse neuroimaging techniques are helping clarify the mechanisms through which inflammation acts on the brain to reorient behavior and predispose to mental and physical illnesses.

Child and adolescent psychiatry is a relatively young field and the recognition, classification, and treatment of disorders in children and adolescents lag behind those in adults. In recent years there is an increasing awareness of the differences between children and adults in psychopathology and pharmacology. Related to this new paediatric regulations have been introduced. This article reviews the regulatory and legislative measures that were adopted in the EU in 2007 and the subsequent impact of these measures on the field of paediatric psychopharmacology. The consequences of the paediatric regulation in the EU are reflected in several domains: regulatory, research aimed at drug development and clinical practices. In the regulatory domain, the consequences include: new paediatric indications, inclusion of special (class) warnings, specification of dose regimens, and information on safety specific to children and adolescents, and development of new medicinal formulations. The paediatric regulation leads to timely development of paediatric friendly formulations and better quality of the clinical evidence. In clinical practices, an increased awareness of the uniqueness of paediatric pharmacology is emerging among medical professionals, and subsequent improvement of medical care (i.e. correct doses, appropriate formulation, monitoring for expected adverse events). In addition, clinical guidelines will have to be revised more frequently in order to integrate the recently acquired knowledge. The new regulations stimulate transparency and discussions between academia, pharmaceutical industry, and regulators. The purpose is to optimize clinical research and obtain evidence for paediatric psychopharmacology, thereby providing adequate support for treatment.

Despite advances in psychopharmacology over the past several decades, treatment outcomes for depression have not substantially improved. Depression is not being eradicated. If anything, the evidence suggests that the problem of depression and treatment-resistant depression is growing, not shrinking. As biologically reductionistic approaches dominate psychiatric practice, patient care has steered away from considering the potent effects of meaning and relationships in the psychopharmacologic treatment of our patients. By construing patients as passive recipients of concrete, specific, and straightforward medical interventions, the field has succumbed to a delusion of precision, and unwittingly moved into an era of treatment resistance in which some of our most potent tools are wasted. In such a model we have settled for treating a disorder rather than a whole person. This article is intended as a step toward remedy. Meaning effects, therapeutic alliance, ambivalence, and patient autonomy, among others, have a powerful and measurable impact on the use of medication that should be considered if we are to treat the whole person. Bringing these elements together into a coherent model of treatment, however, is only a starting point. More research is needed if we are to understand the effects these elements have when used together in an integrated model that is simultaneously personalized and evidence-based.

The physical intensity of a sound, usually expressed in dB on a logarithmic ratio scale, can easily be measured using technical equipment. Loudness is the perceptual correlate of sound intensity, and is usually determined by means of some sort of psychophysical scaling procedure. The interrelation of sound intensity and perceived loudness is still a matter of debate, and the physiological correlate of loudness perception in the human auditory pathway is not completely understood. Various studies indicate that the activation in human auditory cortex is more a representation of loudness sensation rather than of physical sound pressure level. This raises the questions (1), at what stage or stages in the ascending auditory pathway is the transformation of the physical stimulus into its perceptual correlate completed, and (2), to what extent other factors affecting individual loudness judgements might modulate the brain activation as registered by auditory neuroimaging. An overview is given about recent studies on the effects of sound intensity, duration, bandwidth and individual hearing status on the activation in the human auditory system, as measured by various approaches in auditory neuroimaging. This article is part of a Special Issue entitled Human Auditory Neuroimaging.

Rapidly evolving neuroimaging techniques are producing unprecedented quantities of digital data at the same time that many research studies are evolving into global, multi-disciplinary collaborations between geographically distributed scientists. While networked computers have made it almost trivial to transmit data across long distances, collecting and analyzing this data requires extensive metadata if the data is to be maximally shared. Though it is typically straightforward to encode text and numerical values into files and send content between different locations, it is often difficult to attach context and implicit assumptions to the content. As the number of and geographic separation between data contributors grows to national and global scales, the heterogeneity of the collected metadata increases and conformance to a single standardization becomes implausible. Neuroimaging data repositories must then not only accumulate data but must also consolidate disparate metadata into an integrated view. In this article, using specific examples from our experiences, we demonstrate how standardization alone cannot achieve full integration of neuroimaging data from multiple heterogeneous sources and why a fundamental change in the architecture of neuroimaging data repositories is needed instead.

Norepinephrine (NE), octopamine (OA) and phenethylamine (PEA) are easily destroyed by M.A.O. but we could show, even injected intraperitoneally that they are active upon tests used generally to reveal an "antidepressant" effect. This effect is especially studied by using antagonism of apomorphine, reserpine, oxotremorine-induced hypothermia. The psychopharmacological spectra of NE and OA are close to the one of salbutamol and the observed effects correspond to alpha- and beta-adrenergic stimulations. The PEA spectrum is similar to the one of amphetamine and the observed effects correspond to adrenergic stimulations and to a dopaminergic stimulation. The mechanisms involved in the tests realized to show an "antidepressant" effect could reflect an activity not only through endogeneous NA but also possibly through endogeneous OA and PEA.

Research in the area of herbal psychopharmacology has increased markedly over the past decades. To date however, a comprehensive review of herbal antidepressant, anxiolytic and hypnotic psychopharmacology and applications in depression, anxiety and insomnia has been absent. A search of MEDLINE (PubMed), CINAHL, PsycINFO, and the Cochrane Library databases was conducted (up to February 21st 2011) on commonly used psychotropic herbal medicines. A review of the literature was conducted to ascertain mechanisms of action of these botanicals, in addition to a systematic review of controlled clinical trials for treatment of mood, anxiety and sleep disorders, which are common comorbid psychiatric disorders. Specific emphasis was given to emerging phytomedicines. Analysis of evidence levels was conducted, as were effect sizes (Cohen's d) where data were available. Results provided evidence of a range of neurochemical, endocrinological, and epigenetic effects for 21 individual phytomedicines, which are detailed in this paper. Sixty six controlled studies were located involving eleven phytomedicines. Several of these provide a high level of evidence, such as Hypericum perforatum for major depression, and Piper methysticum for anxiety disorders. Several human clinical trials provide preliminary positive evidence of antidepressant effects (Echium amoenum, Crocus sativus, and Rhodiola rosea) and anxiolytic activity (Matricaria recutita, Ginkgo biloba, Passiflora incanata, E. amoenum, and Scutellaria lateriflora). Caution should however be taken when interpreting the results as many studies have not been replicated. Several herbal medicines with in vitro and in vivo evidence are currently unexplored in human studies, and along with use of emerging genetic technologies "herbomics", are areas of potential future research.

There is considerable evidence that neuroimaging findings can improve the early diagnosis of Wernicke's encephalopathy (WE) in clinical settings. The most distinctive neuroimaging finding of acute WE are cytotoxic edema and vasogenic edema, which are represented by bilateral symmetric hyperintensity alterations on T2-weighted MR images in the periphery of the third ventricle, periaqueductal area, mammillary bodies and midbrain tectal plate. An initial bout of WE can result in Korsakoff's syndrome (KS), but repeated bouts in conjunction with its typical comorbidity, chronic alcoholism, can result in signs of tissue degeneration in vulnerable brain regions. Chronic abnormalities identified with neuroimaging enable examination of brain damage in living patients with KS and have expanded the understanding of the neuropsychological deficits resulting from thiamine deficiency, alcohol neurotoxicity, and their comorbidity. Brain structure and functional studies indicate that the interactions involving the thalamus, mammillary bodies, hippocampus, frontal lobes, and cerebellum are crucial for memory formation and executive functions, and the interruption of these circuits by WE and chronic alcoholism can contribute substantially to the neuropsychological deficits in KS.

Background Attention-deficit/hyperactivity symptoms have repeatedly been associated with poor cognitive functioning. Genetic studies have demonstrated a shared etiology of attention-deficit/hyperactivity disorder (ADHD) and cognitive ability, suggesting a common underlying neurobiology of ADHD and cognition. Further, neuroimagingstudies suggest that altered cortical development is related to ADHD. In a large population-based sample we investigated whether cortical morphology, as a potential neurobiological substrate, underlies the association between attention-deficit/hyperactivity symptoms and cognitive problems. Methods The sample consisted of school-aged children with data on attention-deficit/hyperactivity symptoms, cognitive functioning and structural imaging. First, we investigated the association between attention-deficit/hyperactivity symptoms and different domains of cognition. Next, we identified cortical correlates of attention-deficit/hyperactivity symptoms and related cognitive domains. Finally, we studied the role of cortical thickness and gyrification in the behaviour–cognition associations. Results We included 776 children in our analyses. We found that attention-deficit/hyperactivity symptoms were associated specifically with problems in attention and executive functioning (EF; b = −0.041, 95% confidence interval [CI] −0.07 to −0.01, p = 0.004). Cortical thickness and gyrification were associated with both attention-deficit/hyperactivity symptoms and EF in brain regions that have been previously implicated in ADHD. This partly explained the association between attention-deficit/hyperactivity symptoms and EF (bindirect = −0.008, bias-corrected 95% CI −0.018 to −0.001). Limitations The nature of our study did not allow us to draw inferences regarding temporal associations; longitudinal studies are needed for clarification. Conclusion In a large, population-based sample of children, we identified a shared cortical morphology underlying

With recent advances in neuroimaging technology, it is now possible to image human brain function in vivo, which revolutionized the cognitive neuroscience field. However, like any other newly developed technique, the acquisition of neuroimaging data is costly and logistically challenging. Furthermore, studying human cognition requires acquiring a large amount of neuroimaging data, which might not be feasible to do by every researcher in the field. Here, we describe our group's efforts to acquire one of the largest neuroimaging datasets that aims to investigate the neural substrates of age-related cognitive decline, which will be made available to share with other investigators. Our neuroimaging repository includes up to 14 different functional images for more than 486 subjects across the entire adult lifespan in addition to their 3 structural images. Currently, data from 234 participants have been acquired, including all 14 functional and 3 structural images, which is planned to increased to 375 participants in the next few years. A complete battery of neuropsychological tests was also administered to all participants. The neuroimaging and accompanying psychometric data will be available through an online and easy-to-use data sharing website.

There is significant variation in prescriptions among countries in clinical practice for the treatment of comorbidities associated with autism spectrum disorder (ASD). It has been suggested that many people with mental health disorders in low-/middle-income countries do not receive adequate treatment. Hence, this study investigated psychopharmacological treatment patterns for ASD comorbidities in 30 countries and the association between country's income and prescription rates. The IMS Prescribing Insights database was used to investigate prescription patterns for ASD comorbidity treatment from 2007 to 2012. Data were obtained from 30 countries in continents of Europe, Asia, Oceania, Central America, South America, and Africa. The gross domestic product (GDP) per capita was used as a proxy for each country's income. Spearman correlation was used to examine the association between prescription rate and GDP per capita. The highest prescription rates were found in Western Europe (3.89-36.36/10,000) while the lowest prescription rates were found in Asian countries, such as Turkey, Indonesia, Saudi Arabia, and Pakistan (0.04-0.82/10,000). The most commonly prescribed drug for ASD comorbidity treatment in most of the countries was risperidone, but antidepressants and antiepileptic drugs were also frequently prescribed. There was a significant positive correlation between GDP per capita and prescription rate (Spearman ρ = 0.60; P = 0.0011; 95% confidence interval 0.27-0.81), that is, the higher the GDP per capita, the higher the prescription rate. There are marked international differences in prescription rates, and this is partially accounted by economic factors. Future research should combine more data for ASD comorbidity treatment to explore the disparity of psychopharmacological treatment between countries.

Background Theobromine, a methylxanthine related to caffeine and present in high levels in cocoa, may contribute to the appeal of chocolate. However, currently evidence for this is limited. Objectives We conducted a within-subjects placebo-controlled study of a wide range of oral theobromine doses (250, 500, and 1000 mg) using an active control dose of caffeine (200 mg) in 80 healthy participants. Results Caffeine had the expected effects on mood including feelings of alertness, and cardiovascular parameters. Theobromine responses differed according to dose: it showed limited subjective effects at 250 mg and negative mood effects at higher doses. It also dose-dependently increased heart rate. In secondary analyses we also examined individual differences in the drugs' effects in relation to genes related to their target receptors, but few associations were detected. Conclusions This study represents the highest dose of theobromine studied in humans. We conclude that theobromine at normal intake ranges may contribute to the positive effects of chocolate, but at higher intakes effects become negative. PMID:23420115

Neuropsychiatric disorders and syndromes may be underdiagnosed and inadequately treated in individuals infected with HIV. Depression in particular is among the most prevalent diagnoses, and data from controlled clinical studies have shown that antidepressant medications are efficacious and safe for treating depression in HIV-infected persons. A significant shortcoming of this literature is that most of the available data are from studies conducted before the advent of highly active antiretroviral therapy. In addition, apart from antidepressant medications, controlled studies systematically assessing efficacy and safety issues for other classes of psychotropic drugs (e.g., antipsychotic and anxiolytic medications) in HIV-infected persons are lacking. This review summarizes essential findings pertaining to the use of psychotropic medications to treat depression and other neuropsychiatric disorders in the context of HIV. It includes a discussion of clinically relevant treatment considerations (e.g., side effects, drug-drug interactions) derived from the existing literature as well as judgments that clinicians face in the absence of research data. Despite some shortcomings of the existing literature, overall there is compelling evidence that the appropriate use of psychotropic medications (coupled with behavioral therapy) can improve the quality of life of mentally ill HIV-infected individuals.

Context 40–60% of unmedicated depressed individuals respond to Cognitive Therapy (CT) in controlled trials. Multiple previous studies suggest that activity in the subgenual anterior cingulate predicts outcome in CT for depression, but there have been no prospective replications. Objective This study prospectively examined whether subgenual cingulate activity is a reliable and robust prognostic outcome marker for CT for depression and whether its activity changes in treatment. Design Two inception cohorts were assessed with fMRI on different scanners on a task sensitive to sustained emotional information processing before and after 16–20 sessions of CT, along with a sample of control participants tested at comparable intervals. Setting Therapy took place in a hospital outpatient clinic. Patients Participants included 49 unmedicated depressed adults and 35 healthy control participants. Main Outcome Measures Pre-treatment subgenual anterior cingulate activity in an a priori region in response to negative words was correlated with residual severity and used to classify response and remission. Results As expected, in both samples, participants with the lowest pre-treatment sustained subgenual cingulate (sgACC; BA25) reactivity in response to negative words displayed the most improvement in CT (R2=.29, >75% correct classification of response, >70% correct classification of remission). Other a priori regions explained additional variance. Response/Remission in Cohort 2 was predicted based on thresholds from Cohort 1. sgACC activity remained low for remitters following treatment. Conclusions Neuroimaging provides a quick, valid, and clinically applicable way of assessing neural systems associated with treatment response/remission. sgACC activity, in particular, may reflect processes which interfere with treatment, e.g,. emotion generation in addition to its putative regulatory role; alternately, its absence may facilitate treatment response. PMID:22945620

In 1952, the Diagnostic and Statistical Manual of Mental Disorders (DSM) system of creating, validating, studying and employing a diagnostic system in clinical psychiatric practice was introduced. There have been several updates and revisions to this manual and, regardless of its a theoretical framework, it actually does have a framework and presupposition. Essentially the DSM dictates that all psychiatric disorders are syndromes, or a collection of symptoms that commonly occur together and impair psychosocial functioning. These syndromes allow for homogenous groups of patients to be studied and psychotherapies and pharmacotherapies to be developed. This editorial will examine the DSM system with regards to its applicability to central nervous system dysfunction where psychiatric disorders are concerned. Specifically, the brain does not follow categorical, or syndromal, constructs. In fact, the psychiatric patient likely inherits several risk genes that promote abnormal proteins along several neuropathways in the brain. These abnormalities create dysfunctional neurocircuits which create individual psychiatric symptoms, but not a categorical syndrome or diagnosis. The concept that the DSM may be excellent for clinical diagnostic purposes, but less correct in its assumptions for a psychopharmacologist's treatment approaches will be discussed. PMID:23678236

We generated dose-response data for the endogenous and ultra-short-acting hallucinogen, N,N-dimethyltryptamine (DMT), in a cohort of experienced hallucinogen users, measuring multiple biological and psychological outcome measures. Subjective responses were quantified with a new rating scale, the HRS, which provided better resolution of dose effects than did the biological variables. A tolerance study then was performed, in which volunteers received four closely spaced hallucinogenic doses of DMT. Subjective responses demonstrated no tolerance, while biological measures were inconsistently reduced over the course of the sessions. Thus, DMT remains unique among classic hallucinogens in its inability to induce tolerance to its psychological effects. To assess the role of the 5-HT1A site in mediating DMT's effects, a pindolol pre-treatment study was performed. Pindolol significantly increased psychological responses to DMT, suggesting a buffering effect of 5-HT1A agonism on 5-HT2-mediated psychedelic effects. These data are opposite to those described in lower animal models of hallucinogens' mechanisms of action.

Social communication requires shared representations as well as a cognitive flexibility for successful interactions between self and other. What neural mechanisms underlie the ability to distinguish between our own perspective vs. the perspective of others at a conceptual level? In this PET study subjects who were medical students were asked according to the experimental conditions to respond to a list of health-related questions, taking either their own perspective or the perspective of a 'lay person'. Third-person perspective as compared to first-person perspective was associated with activation in the medial part of the superior frontal gyrus, in the left superior temporal sulcus, in the left temporal pole and in the right inferior parietal lobe. The reverse comparison revealed a specific activation in the postcentral gyrus for the first-person conceptual perspective. This study provides congruent results at the conceptual level with previous studies investigating the neural correlates of self/other distinction at the motor level, and opens a new area of research in which conceptual cognition can be viewed in the continuity of motor cognition.

Apolipoprotein E (APOE) ε4 allele is the genetic risk factor with the most established evidence for sporadic Alzheimer's disease. Previous neuroimagingstudies have demonstrated insufficiently consistent functional and structural changes among healthy APOE ε4 carriers when compared to non-carriers. Here, in a cognitively intact elderly group (a total of 110: 45 APOE ε4 carriers, 65 non-carriers), we aimed to investigate the potential role of APOE ε4 in the modulation of grey matter activity, white matter integrity, and brain morphology before the development of clinically significant symptoms and signs, by methods of: amplitude of low frequency fluctuations and regional homogeneity analysis based on resting state fMRI, and fiber tractography approach based on diffusion tensor imaging. Our results revealed that compared to non-carriers, APOE ε4 carriers showed: (1) an inconsistent pattern of activity change in the default mode network, including increased gray matter activity in anterior cingulate cortex and medial prefrontal cortex and decreased activity in precuneus; (2) lower mean diffusivity (MD) in fibers of corona radiata and corpus callosum, and lower axial diffusivity in genu of corpus callosum; and (3) significant positive correlation between the MD value of the right superior corona radiate and gross white matter volume; significant negative correlation between the MD value of the right superior corona radiate and Mini-Mental State Examination (MMSE) score. Our results suggested that APOE ε4 gene can modulate gray matter activity and white matter integrity in cognitive and memory related regions, even before any clinical or neuropsychic symtoms or signs of imminent disease.

It has been hypothesized that the relatively rare autosomal dominant Alzheimer disease (ADAD) may be a useful model of the more frequent, sporadic, late-onset AD (LOAD). Individuals with ADAD have a predictable age at onset and the biomarker profile of ADAD participants in the preclinical stage may be used to predict disease progression and clinical onset. However, the extent to which the pathogenesis and neuropathology of ADAD overlaps with that of LOAD is equivocal. To address this uncertainty, two multicenter longitudinal observational studies, the Alzheimer Disease Neuroimaging Initiative (ADNI) and the Dominantly Inherited Alzheimer Network (DIAN), leveraged the expertise and resources of the existing Knight Alzheimer Disease Research Center (ADRC) at Washington University School of Medicine, St. Louis, Missouri, USA, to establish a Neuropathology Core (NPC). The ADNI/DIAN-NPC is systematically examining the brains of all participants who come to autopsy at the 59 ADNI sites in the USA and Canada and the 14 DIAN sites in the USA (eight), Australia (three), UK (one) and Germany (two). By 2014, 41 ADNI and 24 DIAN autopsies (involving nine participants and 15 family members) had been performed. The autopsy rate in the ADNI cohort in the most recent year was 93% (total since NPC inception: 70%). In summary, the ADNI/DIAN NPC has implemented a standard protocol for all sites to solicit permission for brain autopsy and to send brain tissue to the NPC for a standardized, uniform and state-of-the-art neuropathologic assessment. The benefit to ADNI and DIAN of the implementation of the NPC is very clear. The NPC provides final "gold standard" neuropathological diagnoses and data against which the antecedent observations and measurements of ADNI and DIAN can be compared.

Introduction Major depressive disorder (MDD) is widely prevalent and severely disabling, mainly due to its recurrent nature. A better understanding of the mechanisms underlying MDD-recurrence may help to identify high-risk patients and to improve the preventive treatment they need. MDD-recurrence has been considered from various levels of perspective including symptomatology, affective neuropsychology, brain circuitry and endocrinology/metabolism. However, MDD-recurrence understanding is limited, because these perspectives have been studied mainly in isolation, cross-sectionally in depressed patients. Therefore, we aim at improving MDD-recurrence understanding by studying these four selected perspectives in combination and prospectively during remission. Methods and analysis In a cohort design, we will include 60 remitted, unipolar, unmedicated, recurrent MDD-participants (35–65 years) with ≥2 MDD-episodes. At baseline, we will compare the MDD-participants with 40 matched controls. Subsequently, we will follow-up the MDD-participants for 2.5 years while monitoring recurrences. We will invite participants with a recurrence to repeat baseline measurements, together with matched remitted MDD-participants. Measurements include questionnaires, sad mood-induction, lifestyle/diet, 3 T structural (T1-weighted and diffusion tensor imaging) and blood-oxygen-level-dependent functional MRI (fMRI) and MR-spectroscopy. fMRI focusses on resting state, reward/aversive-related learning and emotion regulation. With affective neuropsychological tasks we will test emotional processing. Moreover, we will assess endocrinology (salivary hypothalamic-pituitary-adrenal-axis cortisol and dehydroepiandrosterone-sulfate) and metabolism (metabolomics including polyunsaturated fatty acids), and store blood for, for example, inflammation analyses, genomics and proteomics. Finally, we will perform repeated momentary daily assessments using experience sampling methods at baseline. We

Manganese (Mn) is an essential metal and has important physiological functions for human health. However, exposure to excess levels of Mn in occupational settings or from environmental sources has been associated with a neurological syndrome comprising cognitive deficits, neuropsychological abnormalities and parkinsonism. Historically, studies on the effects of Mn in humans and experimental animals have been concerned with effects on the basal ganglia and the dopaminergic system as it relates to movement abnormalities. However, emerging studies are beginning to provide significant evidence of Mn effects on cortical structures and cognitive function at lower levels than previously recognized. This review advances new knowledge of putative mechanisms by which exposure to excess levels of Mn alters neurobiological systems and produces neurological deficits not only in the basal ganglia but also in the cerebral cortex. The emerging evidence suggests that working memory is significantly affected by chronic Mn exposure and this may be mediated by alterations in brain structures associated with the working memory network including the caudate nucleus in the striatum, frontal cortex and parietal cortex. Dysregulation of the dopaminergic system may play an important role in both the movement abnormalities as well as the neuropsychiatric and cognitive function deficits that have been described in humans and non-human primates exposed to Mn. PMID:23805100

Schizophrenia is a severe, chronic, and strongly disabling neuropsychiatric disorder, characterized by cognitive decline, positive and negative symptoms. Positive symptoms respond well to antipsychotic medication and psycho-social interventions, in contrast to negative symptoms and neurocognitive impairments. Cognitive deficits have been linked to a poorer outcome and hence specific cognitive remediation therapies have been proposed. Their effectiveness is nowadays approved and neurobiological correlates have been reconfirmed by brain imaging studies. Interestingly, recent MRI work showed that commercial video games modified similar brain areas as these specialized training programs. If gray matter increases and functional brain modulations would translate in better cognitive and every day functioning, commercial video game training could be an enjoyable and economically interesting treatment option for patients with neuropsychiatric disorders. This systematic review summarizes advances in the area with emphasis on imaging studies dealing with brain changes upon video game training and contrasts them to conventional cognitive remediation. Moreover, we discuss potential challenges therapeutic video game development and research would have to face in future treatment of schizophrenia.

Many studies have assessed the neural underpinnings of creativity, failing to find a clear anatomical localization. We aimed to provide evidence for a multi-componential neural system for creativity. We applied a general activation likelihood estimation (ALE) meta-analysis to 45 fMRI studies. Three individual ALE analyses were performed to assess creativity in different cognitive domains (Musical, Verbal, and Visuo-spatial). The general ALE revealed that creativity relies on clusters of activations in the bilateral occipital, parietal, frontal, and temporal lobes. The individual ALE revealed different maximal activation in different domains. Musical creativity yields activations in the bilateral medial frontal gyrus, in the left cingulate gyrus, middle frontal gyrus, and inferior parietal lobule and in the right postcentral and fusiform gyri. Verbal creativity yields activations mainly located in the left hemisphere, in the prefrontal cortex, middle and superior temporal gyri, inferior parietal lobule, postcentral and supramarginal gyri, middle occipital gyrus, and insula. The right inferior frontal gyrus and the lingual gyrus were also activated. Visuo-spatial creativity activates the right middle and inferior frontal gyri, the bilateral thalamus and the left precentral gyrus. This evidence suggests that creativity relies on multi-componential neural networks and that different creativity domains depend on different brain regions. PMID:26322002

Background and Objective: People with amnestic mild cognitive impairment (aMCI) are at a higher risk of developing Alzheimers Dementia (AD) than their cognitively normal peers. Decreased glucose metabolism with F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) is a downstream marker of neuronal injury and neurodegeneration. The risk of developing AD is higher in patients with aMCI who have a pattern of AD related glucose metabolic changes on FDG-PET than those who do not have these changes. We evaluated the utility of visual and ‘statistical parametric mapping (SPM)-supported reading’ of the FDG-PET scans of patients clinically classified as aMCI for identification of predementia patterns and for prediction of their progression to AD (PTAD). Patients and Methods: A total of 35 patients diagnosed as aMCI (mini mental state examination (MMSE) score ≥ 25) at the cognitive disorders and memory (CDM) clinic of speciality neurology centers were referred for a resting FDG-PET study. All patients had a detailed neurological, neuropsychological, and magnetic resonance imaging (MRI) evaluation prior to referral. Mean age of patients was 67.9 ± 8.7 (standard deviation (SD)) years, male: female (M: F) =26:9. Twenty healthy age-matched controls were included in the study for SPM (http://www.fil.ion.ucl.ac.uk/spm/). Scans were interpreted visually and using SPM. Each scan was classified as high, intermediate, or low likelihood for PTAD. Results: On visual analysis, four scans were classified as high likelihood of PTAD and reveled hypometabolism in AD related territories. Seven patients had hypometabolism in at least one AD related territory and were classified as intermediate likelihood for PTAD. Two patients had hypometabolism in other than AD territories, while 22 patients did not show any significant hypometabolism on their FDG-PET scans and were classified as low likelihood for PTAD. SPM analysis of these cases confirmed the areas hypometabolism in all

There is now compelling evidence that motor imagery (MI) promotes motor learning. While MI has been shown to influence the early stages of the learning process, recent data revealed that sleep also contributes to the consolidation of the memory trace. How such “online” and “offline” processes take place and how they interact to impact the neural underpinnings of movements has received little attention. The aim of the present review is twofold: (i) providing an overview of recent applied and fundamental studies investigating the effects of MI practice (MIP) on motor learning; and (ii) detangling applied and fundamental findings in support of a sleep contribution to motor consolidation after MIP. We conclude with an integrative approach of online and offline learning resulting from intense MIP in healthy participants, and underline research avenues in the motor learning/clinical domains. PMID:27445755

Previous research has demonstrated that sport-related concussions can have short-term effects on cognitive processes, but the long-term consequences are less understood and warrant more research. This study was the first to use event-related functional magnetic resonance imaging (fMRI) to examine long-term differences in neural activity during memory tasks in former athletes who have sustained multiple sport-related concussions. In an event-related fMRI study, former football players reporting multiple sport-related concussions (i.e., three or more) were compared with players who reported fewer than three concussions during a memory paradigm examining item memory (i.e., memory for the particular elements of an event) and relational memory (i.e., memory for the relationships between elements). Behaviorally, we observed that concussion history did not significantly affect behavioral performance, because persons in the low and high concussion groups had equivalent performance on both memory tasks, and in addition, that concussion history was not associated with any behavioral memory measures. Despite demonstrating equivalent behavioral performance, the two groups of former players demonstrated different neural recruitment patterns during relational memory retrieval, suggesting that multiple concussions may be associated with functional inefficiencies in the relational memory network. In addition, the number of previous concussions significantly correlated with functional activity in a number of brain regions, including the medial temporal lobe and inferior parietal lobe. Our results provide important insights in understanding the long-term functional consequences of sustaining multiple sports-related concussions.

Abstract Previous research has demonstrated that sport-related concussions can have short-term effects on cognitive processes, but the long-term consequences are less understood and warrant more research. This study was the first to use event-related functional magnetic resonance imaging (fMRI) to examine long-term differences in neural activity during memory tasks in former athletes who have sustained multiple sport-related concussions. In an event-related fMRI study, former football players reporting multiple sport-related concussions (i.e., three or more) were compared with players who reported fewer than three concussions during a memory paradigm examining item memory (i.e., memory for the particular elements of an event) and relational memory (i.e., memory for the relationships between elements). Behaviorally, we observed that concussion history did not significantly affect behavioral performance, because persons in the low and high concussion groups had equivalent performance on both memory tasks, and in addition, that concussion history was not associated with any behavioral memory measures. Despite demonstrating equivalent behavioral performance, the two groups of former players demonstrated different neural recruitment patterns during relational memory retrieval, suggesting that multiple concussions may be associated with functional inefficiencies in the relational memory network. In addition, the number of previous concussions significantly correlated with functional activity in a number of brain regions, including the medial temporal lobe and inferior parietal lobe. Our results provide important insights in understanding the long-term functional consequences of sustaining multiple sports-related concussions. PMID:23679098

Background: There is accumulating evidence on the negative impacts of childhood poverty on physical and mental health. Previous work has suggested hyperactive neural response to social fear cues, as well as impairment in neural regulatory functions. However, despite differences found between males and females in stress-related and anxiety disorders, possible sex-specific effects of poverty on emotional processing have not been explored. Methods: We analyzed data from three previously reported experiments of childhood poverty effects on emotional processing and regulation, for sex-specific effects. Participants were 52 healthy Caucasian males and females, from a longitudinal cohort of poverty development study, who were recruited for examining the long-term effects of childhood poverty and stress. The three functional MRI studies included emotion regulation task, emotional face assessment task, and shifted attention emotion appraisal task. Brain activations that associated with childhood poverty previously were entered into a regression analysis with interaction of gender by childhood income-to-need ratio as the independent variable, and age and current income-to-need ratio as variables of no interest, separately for males and females. Results: Amygdala reactivity to implicitly processed fearful faces was positively correlated with childhood income-to-need in adult females but not males. On the other hand, activation in dorsolateral and ventrolateral prefrontal regions during emotion regulation by reappraisal was positively correlated with childhood income-to-need in males. Conclusion: Childhood poverty may exert sex-specific effects in adulthood as presented by hypersensitive emotional reactivity of the amygdala in females, and impaired emotion regulatory function of the prefrontal cortex in males. Results suggest further focus on sex-specific effects of childhood poverty. PMID:27973443

The vulnerability to suicidal behavior has been modeled in deficits in both valuation and cognitive control processes, mediated by ventral and dorsal prefrontal cortices. To uncover potential markers of suicidality based on this model, we measured several brain morphometric parameters using 1.5T magnetic resonance imaging in a large sample and in a specifically designed study. We then tested their classificatory properties. Three groups were compared: euthymic suicide attempters with a past history of mood disorders and suicidal behavior (N=67); patient controls with a past history of mood disorders but not suicidal behavior (N=82); healthy controls without any history of mental disorder (N=82). A hypothesis-driven region-of-interest approach was applied targeting the orbitofrontal cortex (OFC), ventrolateral (VLPFC), dorsal (DPFC) and medial (including anterior cingulate cortex; MPFC) prefrontal cortices. Both voxel-based (SPM8) and surface-based morphometry (Freesurfer) analyses were used to comprehensively evaluate cortical gray matter measure, volume, surface area and thickness. Reduced left VLPFC volume in attempters vs both patient groups was found (P=0.001, surviving multiple comparison correction, Cohen's d=0.65 95% (0.33-0.99) between attempters and healthy controls). In addition, reduced measures in OFC and DPFC, but not MPFC, were found with moderate effect sizes in suicide attempters vs healthy controls (Cohen's d between 0.34 and 0.52). Several of these measures were correlated with suicidal variables. When added to mood disorder history, left VLPFC volume increased within-sample specificity in identifying attempters in a significant but limited way. Our study, therefore, confirms structural prefrontal alterations in individuals with histories of suicide attempts. A future clinical application of these markers will, however, necessitate further research.

The vulnerability to suicidal behavior has been modeled in deficits in both valuation and cognitive control processes, mediated by ventral and dorsal prefrontal cortices. To uncover potential markers of suicidality based on this model, we measured several brain morphometric parameters using 1.5T magnetic resonance imaging in a large sample and in a specifically designed study. We then tested their classificatory properties. Three groups were compared: euthymic suicide attempters with a past history of mood disorders and suicidal behavior (N=67); patient controls with a past history of mood disorders but not suicidal behavior (N=82); healthy controls without any history of mental disorder (N=82). A hypothesis-driven region-of-interest approach was applied targeting the orbitofrontal cortex (OFC), ventrolateral (VLPFC), dorsal (DPFC) and medial (including anterior cingulate cortex; MPFC) prefrontal cortices. Both voxel-based (SPM8) and surface-based morphometry (Freesurfer) analyses were used to comprehensively evaluate cortical gray matter measure, volume, surface area and thickness. Reduced left VLPFC volume in attempters vs both patient groups was found (P=0.001, surviving multiple comparison correction, Cohen's d=0.65 95% (0.33–0.99) between attempters and healthy controls). In addition, reduced measures in OFC and DPFC, but not MPFC, were found with moderate effect sizes in suicide attempters vs healthy controls (Cohen's d between 0.34 and 0.52). Several of these measures were correlated with suicidal variables. When added to mood disorder history, left VLPFC volume increased within-sample specificity in identifying attempters in a significant but limited way. Our study, therefore, confirms structural prefrontal alterations in individuals with histories of suicide attempts. A future clinical application of these markers will, however, necessitate further research. PMID:25710122

Background Individuals at clinical high-risk (CHR) who progress to fully psychotic symptoms have been observed to show a steeper rate of cortical gray matter reduction compared with those without symptomatic progression and with healthy controls. Whether such changes reflect processes associated with the pathophysiology of schizophrenia or exposure to antipsychotic drugs is unknown. Methods In this multisite study, 274 CHR cases, including 35 who converted to psychosis, and 135 healthy comparison subjects were scanned with MRI at baseline, 12-month follow-up, and/or the point of conversion for those who developed fully psychotic symptoms. Results In a traveling subjects sub-study, we observed excellent reliability for measures of cortical thickness and subcortical volumes. Controlling for multiple comparisons throughout the brain, CHR converters showed a steeper rate of gray matter loss in right superior frontal, middle frontal, and medial orbitofrontal cortical regions, as well as a greater rate of expansion of the third ventricle, compared with CHR non-converters and healthy controls. Differential tissue loss was present among cases who had not received antipsychotic medications during the inter-scan interval and was predicted by baseline levels of an aggregate measure of pro-inflammatory cytokines in plasma. Conclusions These findings demonstrate that the brain changes are not explained by exposure to antipsychotic drugs, but likely play a role in psychosis pathophysiology. Given that the cortical changes were more pronounced among cases with briefer durations of prodromal symptoms, contributing factors may predominantly play a role in acute-onset forms of psychosis. PMID:25034946

Longitudinal imaging studies are essential to understanding the neural development of neuropsychiatric disorders, substance use disorders, and normal brain. Using appropriate image processing and statistical tools to analyze the imaging, behavioral, and clinical data is critical for optimally exploring and interpreting the findings from those imaging studies. However, the existing imaging processing and statistical methods for analyzing imaging longitudinal measures are primarily developed for cross-sectional neuroimagingstudies. The simple use of these cross-sectional tools to longitudinal imaging studies will significantly decrease the statistical power of longitudinal studies in detecting subtle changes of imaging measures and the causal role of time-dependent covariate in disease process. The main objective of this paper is to develop longitudinal statistics toolbox, called LSTGEE, for the analysis of neuroimaging data from longitudinal studies. We develop generalized estimating equations for jointly modeling imaging measures with behavioral and clinical variables from longitudinal studies. We develop a test procedure based on a score test statistic and a resampling method to test linear hypotheses of unknown parameters, such as associations between brain structure and function and covariates of interest, such as IQ, age, gene, diagnostic groups, and severity of disease. We demonstrate the application of our statistical methods to the detection of the changes of the fractional anisotropy across time in a longitudinal neonate study. Particularly, our results demonstrate that the use of longitudinal statistics can dramatically increase the statistical power in detecting the changes of neuroimaging measures. The proposed approach can be applied to longitudinal data with multiple outcomes and accommodate incomplete and unbalanced data, i.e., subjects with different number of measurements.

Genetic testing in psychiatric practice may be a beneficial adjunct to the nursing toolbox of considerations used to improve patient outcomes. Since 2004, the psychiatric community has used genotyping to personalize medication options for their patients. Although not a definitive or exact science, pharmacogenetic testing for psychopharmacological treatment options offers nurses and their patients insights into potential treatments that will reduce the current trial-and-error prescribing practices and more quickly improve patients' quality of life. The current article guides nurses through the process of conducting genetic testing, interpreting the results, and applying the results in clinical practice using a fictitious case example. [Journal of Psychosocial Nursing and Mental Health Services, 55(3), 19-23.].

The four Ds of medical malpractice are duty, dereliction (negligence or deviation from the standard of care), damages, and direct cause. Each of these four elements must be proved to have been present, based on a preponderance of the evidence, for malpractice to be found. The principles of psychopharmacology and the information in the package insert for a drug often play a central role in deciding whether dereliction and direct cause for damages were or were not applicable in a particular case. The author uses data from two cases in which patients were inadvertently fatally poisoned by medication to illustrate two ways in which such information can affect the outcome. In one case, the clinician should have known that he was giving a toxic dose to the patient, whereas that was not true in the other case.

The possible role of iron in neurodegeneration was studied by various techniques: electron microscopy, enzyme-linked immunosorbent assay, Mössbauer spectroscopy, atomic absorption, ultrasonography and magnetic resonance imaging. The measurements were made on human tissues extracted from liver and from brain structures involved in diseases of the human brain: substantia nigra (Parkinson’s, PD), hippocampal cortex (Alzheimer’s, AD) and globus pallidus (progressive supranuclear palsy, PSP). The sizes of the iron cores of ferritin, the main iron storage compound in tissues, were found to be smaller in brain than in liver. Brain ferritin has a higher proportion of H to L chains compared to liver. A significant decrease of the concentration of L chains in PD compared to control was found. No increase in the concentration of iron in PD versus control was detected; however, there was an increase of labile iron, which constitutes only 2‰ of brain iron. In AD an increase in the concentration of ferritin was noticed, without a significant increase in iron concentration. In PSP an increase of total iron was observed. Our findings suggest that the mechanisms leading to the death of nerve cells in these three diseases may be different, although all may be related to iron mediated oxidative stress.

Remembering to execute pre-defined intentions at the appropriate time in the future is typically referred to as Prospective Memory (PM). Studies of PM showed that distinct cognitive processes underlie the execution of delayed intentions depending on whether the cue associated with such intentions is focal to ongoing activity processing or not (i.e., cue focality). The present activation likelihood estimation (ALE) meta-analysis revealed several differences in brain activity as a function of focality of the PM cue. The retrieval of intention is supported mainly by left anterior prefrontal cortex (Brodmann Area, BA 10) in nonfocal tasks, and by cerebellum and ventral parietal regions in focal tasks. Furthermore, the precuneus showed increased activation during the maintenance phase of intentions compared to the retrieval phase in nonfocal tasks, whereas the inferior parietal lobule showed increased activation during the retrieval of intention compared to maintenance phase in the focal tasks. Finally, the retrieval of intention relies more on the activity in anterior cingulate cortex for nonfocal tasks, and on posterior cingulate cortex for focal tasks. Such focality-related pattern of activations suggests that prospective remembering is mediated mainly by top-down and stimulus-independent processes in nonfocal tasks, whereas by more automatic, bottom-up, processes in focal tasks. PMID:27185531

Suicidal vulnerability has been related to impaired value-based decision-making and increased sensitivity to social threat, mediated by the prefrontal cortex. Using functional magnetic resonance imaging, we aimed at replicating these previous findings by measuring brain activation during the Iowa Gambling Task and an emotional faces viewing task. Participants comprised 15 euthymic suicide attempters (history of depression and suicidal behavior) who were compared with 23 euthymic patient controls (history of depression without suicidal history) and 35 healthy controls. The following five model-based regions of interest were investigated: the orbitofrontal cortex (OFC), ventrolateral prefrontal cortex (VLPFC), anterior cingulate cortex (ACC), medial (MPFC) and dorsal prefrontal cortex (DPFC). Suicide attempters relative to patient controls showed (1) increased response to angry vs. neutral faces in the left OFC and the VLPFC, as previously reported; (2) increased response to wins vs. losses in the right OFC, DPFC and ACC; (3) decreased response to risky vs. safe choices in the left DPFC; and (4) decreased response to sad vs. neutral faces in the right ACC. This study links impaired valuation processing (here for signals of social threat, sadness and reward) to prefrontal cortex dysfunction in suicide attempters. These long-term deficits may underlie the impaired decision-making and social difficulties found in suicide attempters.

Here we aimed at finding the neural correlates of the general aspect of visual aesthetic experience (VAE) and those more strictly correlated with the content of the artworks. We applied a general activation likelihood estimation (ALE) meta-analysis to 47 fMRI experiments described in 14 published studies. We also performed four separate ALE analyses in order to identify the neural substrates of reactions to specific categories of artworks, namely portraits, representation of real-world-visual-scenes, abstract paintings, and body sculptures. The general ALE revealed that VAE relies on a bilateral network of areas, and the individual ALE analyses revealed different maximal activation for the artworks' categories as function of their content. Specifically, different content-dependent areas of the ventral visual stream are involved in VAE, but a few additional brain areas are involved as well. Thus, aesthetic-related neural responses to art recruit widely distributed networks in both hemispheres including content-dependent brain areas of the ventral visual stream. Together, the results suggest that aesthetic responses are not independent of sensory, perceptual, and cognitive processes.

Background The biomarker model of Alzheimer’s disease (AD) hypothesizes a dynamic sequence of amyloidosis, neurodegeneration, and cognitive decline, as an individual progresses from preclinical AD to dementia. Despite supportive evidence from cross-sectional studies, verification with long-term within-individual data is needed. Methods Autosomal dominant AD (ADAD) mutation carriers, aged 21 years or older (no cognitive restrictions), were recruited from across the United States via referral by colleagues or ADAD families themselves. Sixteen individuals with mutations in PSEN1, PSEN2 or APP, aged 28 to 56, were assessed longitudinally every one to two years, between March 23, 2003 and August 1, 2014. Participants completed two to eight assessments (total=83), over a period of two to eleven years. We measured global amyloid-beta load with Pittsburgh Compound-B PET, posterior cortical metabolism with [18F]fluorodeoxyglucose PET, hippocampal volume (age-, and gender-corrected) with T1 MRI, verbal memory with 10-item delayed word recall, and general cognition with Mini Mental State Exam. We estimated overall biomarker trajectories across estimated years from symptom onset (EYO) using linear mixed models, and compared ADAD estimates to cross-sectional data from cognitively normal, older controls selected to be negative for amyloidosis, hypometabolism, and hippocampal atrophy. In seven individuals with the longest follow-up (seven/eight assessments spanning six to eleven years), we further examined the within-individual progression of amyloidosis, metabolism, hippocampal volume, and cognition, to identify progressive within-individual change in these markers (increase/decrease of greater than two Z-scores standardized to controls). Findings Significant differences in ADAD compared to controls (p<0·01) were detected in the following order: increased amyloidosis (−7.5 EYO), decreased metabolism (0 EYO), decreased hippocampal volume and verbal memory (+7.5 EYO

Objectives Post-graduate training for specialisation in psychiatry and psychotherapy is part of a 4-6-year programme. This paper aims to inform on the general situation of teaching and training of psychopharmacology-psychopharmacotherapy in Europe. It presents the need for a psychopharmacotherapy education in psychiatric training programmes. Arguments as well as a proposal for a catalogue of learning objectives and an outline of a psychopharmacology curriculum are presented. Methods Based on their experience and on an analysis of the literature, the authors, experts in psychopharmacology-pharmacotherapy teaching, critically analyse the present situation and propose the development of a curriculum at the European level. Results Teaching programmes vary widely between European countries and, generally, teaching of psychopharmacology and pharmacotherapy does not exceed two-dozen hours. This is insufficient if one considers the central importance of psychopharmacology. A psychopharmacology-psychopharmacotherapy curriculum for the professional training of specialists in psychiatry and psychotherapy is proposed. Conclusions As the number of hours of theoretical teaching and practical training is insufficient, a catalogue of learning objectives should be established, which would then be part of a comprehensive curriculum at the European level. It could be inspired partly by those few previously proposed by other groups of authors and organisations.

Aldous Huxley's Brave New World is a famous dystopia, frequently called upon in public discussions about new biotechnology. It is less well known that 30 years later Huxley also wrote a utopian novel, called Island. This paper will discuss both novels focussing especially on the role of psychopharmacological substances. If we see fiction as a way of imagining what the world could look like, then what can we learn from Huxley's novels about psychopharmacology and how does that relate to the discussion in the ethical and philosophical literature on this subject? The paper argues that in the current ethical discussion the dystopian vision on psychopharmacology is dominant, but that a comparison between Brave New World and Island shows that a more utopian view is possible as well. This is illustrated by a discussion of the issue of psychopharmacology and authenticity. The second part of the paper draws some further conclusions for the ethical debate on psychopharmacology and human enhancement, by comparing the novels not only with each other, but also with our present reality. It is claimed that the debate should not get stuck in an opposition of dystopian and utopian views, but should address important issues that demand attention in our real world: those of evaluation and governance of enhancing psychopharmacological substances in democratic, pluralistic societies.

FEATURE AT A GLANCE In this article we review recent and potential applications of optical neuroimaging to human factors and usability research. We focus specifically on functional near-infrared spectroscopy (fNIRS) because of its cost-effectiveness and ease of implementation. Researchers have used fNIRS to assess a range of psychological phenomena relevant to human factors, such as cognitive workload, attention, motor activity, and more. It offers the opportunity to measure hemodynamic correlates of mental activity during task completion in human factors and usability studies. We also consider some limitations and future research directions. PMID:28286404

Advances in molecular and structural and functional neuroimaging are rapidly expanding the complexity of neurobiological understanding of Parkinson’s disease (PD). This review article begins with an introduction to PD neurobiology as a foundation for interpreting neuroimaging findings that may further lead to more integrated and comprehensive understanding of PD. Diverse areas of PD neuroimaging are then reviewed and summarized, including positron emission tomography, single photon emission computed tomography, magnetic resonance spectroscopy and imaging, transcranial sonography, magnetoencephalography, and multimodal imaging, with focus on human studies published over the last five years. These included studies on differential diagnosis, co-morbidity, genetic and prodromal PD, and treatments from L-DOPA to brain stimulation approaches, transplantation and gene therapies. Overall, neuroimaging has shown that PD is a neurodegenerative disorder involving many neurotransmitters, brain regions, structural and functional connections, and neurocognitive systems. A broad neurobiological understanding of PD will be essential for translational efforts to develop better treatments and preventive strategies. Many questions remain and we conclude with some suggestions for future directions of neuroimaging of PD. PMID:26409344

The multitude of modern imaging techniques has made pediatric neuroradiology increasingly complex. The practitioner must have a thorough understanding of each possible diagnostic study in order to achieve the best results at the least expense and with minimal risk. In this book, MRI is emphasized; correlative CT, ultrasound, angiographic, and conventional x-ray studies assist in establishing effective diagnostic protocols and reaching accurate diagnoses.

Functional deficits due to traumatic brain injury (TBI) can have significant and enduring consequences upon patients’ life quality and expectancy. Although functional neuroimaging is essential for understanding TBI pathophysiology, an insufficient amount of effort has been dedicated to the task of translating functional neuroimaging findings into information with clinical utility. The purpose of this review is to summarize the use of functional neuroimaging techniques – especially functional magnetic resonance imaging, diffusion tensor imaging, positron emission tomography, magnetic resonance spectroscopy, and electroencephalography – for advancing current knowledge of TBI-related brain dysfunction and for improving the rehabilitation of TBI patients. We focus on seven core areas of functional deficits, namely consciousness, motor function, attention, memory, higher cognition, personality, and affect, and, for each of these, we summarize recent findings from neuroimagingstudies which have provided substantial insight into brain function changes due to TBI. Recommendations are also provided to aid in setting the direction of future neuroimaging research and for understanding brain function changes after TBI. PMID:26396520

Although tinnitus may originate in damage to the peripheral auditory apparatus, its perception and distressing symptomatology are consequences of alterations to auditory, sensory, and limbic neural networks. This has been described in several studies, some using advanced structural MR imaging techniques such as diffusion tensor imaging. An understanding of these complex changes could enable development of targeted treatment. New MR imaging techniques enabling detailed depiction of the labyrinth may be useful when diagnosis of Meniere disease is equivocal. Advances in computed tomography and MR imaging have enabled noninvasive diagnosis of dural arteriovenous fistulae.

Statistical machine learning methods are increasingly used for neuroimaging data analysis. Their main virtue is their ability to model high-dimensional datasets, e.g., multivariate analysis of activation images or resting-state time series. Supervised learning is typically used in decoding or encoding settings to relate brain images to behavioral or clinical observations, while unsupervised learning can uncover hidden structures in sets of images (e.g., resting state functional MRI) or find sub-populations in large cohorts. By considering different functional neuroimaging applications, we illustrate how scikit-learn, a Python machine learning library, can be used to perform some key analysis steps. Scikit-learn contains a very large set of statistical learning algorithms, both supervised and unsupervised, and its application to neuroimaging data provides a versatile tool to study the brain.

The advent of powerful neuroimaging tools such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) has begun to redefine how we diagnose, define, and understand disorders of consciousness such as the vegetative and minimally conscious states. In my paper, I review how research using these methods is both elucidating these brain states and creating diagnostic dilemmas related to their classification as the specificity and sensitivity of traditional behavior-based assessments are weighed against sensitive but not yet fully validated neuroimaging data. I also consider how these methods are being studied as potential communication vectors for therapeutic use in subjects who heretofore have been thought to be unresponsive or minimally conscious. I conclude by considering the ethical challenges posed by novel diagnostic and therapeutic neuroimaging applications and contextualize these scientific developments against the broader needs of patients and families touched by severe brain injury.

In an attempt to increase power to detect genetic associations with brain phenotypes derived from human neuroimaging data, we recently conducted a large-scale, genome-wide association meta-analysis of hippocampal, brain, and intracranial volume through the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium. Here, we present a freely available online interactive tool, EnigmaVis, which makes it easy to visualize the association results generated by the consortium alongside allele frequency, genes, and functional annotations. EnigmaVis runs natively within the web browser, and generates plots that show the level of association between brain phenotypes at user-specified genomic positions. Uniquely, EnigmaVis is dynamic; users can interact with elements on the plot in real time. This software will be useful when exploring the effect on brain structure of particular genetic variants influencing neuropsychiatric illness and cognitive function. Future projects of the consortium and updates to EnigmaVis will also be displayed on the site. EnigmaVis is freely available online at http://enigma.loni.ucla.edu/enigma-vis/

Functional neuroimaging techniques have transformed our ability to probe the neurobiological basis of behaviour and are increasingly being applied by the wider neuroscience community. However, concerns have recently been raised that the conclusions that are drawn from some human neuroimagingstudies are either spurious or not generalizable. Problems such as low statistical power, flexibility in data analysis, software errors and a lack of direct replication apply to many fields, but perhaps particularly to functional MRI. Here, we discuss these problems, outline current and suggested best practices, and describe how we think the field should evolve to produce the most meaningful and reliable answers to neuroscientific questions.

Objective: Neuroimaging techniques are increasingly important in psychiatric research and clinical practice, but few postgraduate psychiatry programs offer formal training in neuroimaging. To address this need, the authors developed a course to prepare psychiatric residents to use neuroimaging techniques effectively in independent practice.…

Abstract Functional brain imaging techniques appear ideally suited to explore the pathophysiology of freezing of gait (FOG). In the last two decades, techniques based on magnetic resonance or nuclear medicine imaging have found a number of structural changes and functional disconnections between subcortical and cortical regions of the locomotor network in patients with FOG. FOG seems to be related in part to disruptions in the “executive-attention” network along with regional tissue loss including the premotor area, inferior frontal gyrus, precentral gyrus, the parietal and occipital areas involved in visuospatial functions of the right hemisphere. Several subcortical structures have been also involved in the etiology of FOG, principally the caudate nucleus and the locomotor centers in the brainstem. Maladaptive neural compensation may present transiently in the presence of acute conflicting motor, cognitive or emotional stimulus processing, thus causing acute network overload and resulting in episodic impairment of stepping. In this review we will summarize the state of the art of neuroimaging research for FOG. We will also discuss the limitations of current approaches and delineate the next steps of neuroimaging research to unravel the pathophysiology of this mysterious motor phenomenon. PMID:25757831

The rapid advancement of neuroimaging methodology and availability has transformed neuroscience research. The answers to many questions that we ask about how the brain is organized depend on the quality of data that we are able to obtain about the locations, dynamics, fluctuations, magnitudes, and types of brain activity and structural changes. In this review, an attempt is made to take a snapshot of the cutting edge of a small component of the very rapidly evolving field of neuroimaging. For each area covered, a brief context is provided along with a summary of a few of the current developments and issues. Then, several outstanding papers, published in the past year or so, are described, providing an example of the directions in which each area is progressing. The areas covered include functional MRI (fMRI), voxel based morphometry (VBM), diffusion tensor imaging (DTI), electroencephalography (EEG), magnetoencephalography (MEG), optical imaging, and positron emission tomography (PET). More detail is included on fMRI, as subsections include: functional MRI interpretation, new functional MRI contrasts, MRI technology, MRI paradigms and processing, and endogenous oscillations in functional MRI. PMID:19338512

Sports-related concussions are one of the major causes of mild traumatic brain injury. Although most patients recover completely within days to weeks, those who experience repetitive brain trauma (RBT) may be at risk for developing a condition known as chronic traumatic encephalopathy (CTE). While this condition is most commonly observed in athletes who experience repetitive concussive and/or subconcussive blows to the head, such as boxers, football players, or hockey players, CTE may also affect soldiers on active duty. Currently, the only means by which to diagnose CTE is by the presence of phosphorylated tau aggregations post-mortem. Non-invasive neuroimaging, however, may allow early diagnosis as well as improve our understanding of the underlying pathophysiology of RBT. The purpose of this article is to review advanced neuroimaging methods used to investigate RBT, including diffusion tensor imaging, magnetic resonance spectroscopy, functional magnetic resonance imaging, susceptibility weighted imaging, and positron emission tomography. While there is a considerable literature using these methods in brain injury in general, the focus of this review is on RBT and those subject populations currently known to be susceptible to RBT, namely athletes and soldiers. Further, while direct detection of CTE in vivo has not yet been achieved, all of the methods described in this review provide insight into RBT and will likely lead to a better characterization (diagnosis), in vivo, of CTE than measures of self-report. PMID:25031630

Sports-related concussions are one of the major causes of mild traumatic brain injury. Although most patients recover completely within days to weeks, those who experience repetitive brain trauma (RBT) may be at risk for developing a condition known as chronic traumatic encephalopathy (CTE). While this condition is most commonly observed in athletes who experience repetitive concussive and/or subconcussive blows to the head, such as boxers, football players, or hockey players, CTE may also affect soldiers on active duty. Currently, the only means by which to diagnose CTE is by the presence of phosphorylated tau aggregations post-mortem. Non-invasive neuroimaging, however, may allow early diagnosis as well as improve our understanding of the underlying pathophysiology of RBT. The purpose of this article is to review advanced neuroimaging methods used to investigate RBT, including diffusion tensor imaging, magnetic resonance spectroscopy, functional magnetic resonance imaging, susceptibility weighted imaging, and positron emission tomography. While there is a considerable literature using these methods in brain injury in general, the focus of this review is on RBT and those subject populations currently known to be susceptible to RBT, namely athletes and soldiers. Further, while direct detection of CTE in vivo has not yet been achieved, all of the methods described in this review provide insight into RBT and will likely lead to a better characterization (diagnosis), in vivo, of CTE than measures of self-report.

There is increased interest in the role that ethnicity, sociocultural factors, and gender play in research, health care delivery, and response to intervention. The impact of these factors on AIDS awareness programs, on the phenomenology of suicide and anorexia nervosa, and on clinical psychopharmacology in a homogeneous population is discussed. Risky sex practices can be related to cultural norms that stigmatize condom use and sex education; economic deprivation; and male dominance. Gender, cultural, and ethnic demographics can identify high-risk groups as well as influence effective interventions. Suicide rates and risk factors are compared in African-American, Canadian Native, and South Korean adolescents. Academic stress was a differential risk factor for the Koreans. Anorexia nervosa predominantly affects women and has cultural differences in prevalence. The homogeneous population in Hong Kong illustrates the impact of ethnicity, sociocultural factors, and gender on clinical psychopharmacology. Attention to ethnicity, sociocultural factors, and gender can individualize and improve the effectiveness of clinical psychopharmacology.

The integration of research on neuroimaging and pharmacogenetics holds promise for improving treatment for neuropsychiatric conditions. Neuroimaging may provide a more sensitive early measure of treatment response in genetically defined patient groups, and could facilitate development of novel therapies based on an improved understanding of pathogenic mechanisms underlying pharmacogenetic associations. This review summarizes progress in efforts to incorporate neuroimaging into genetics and treatment research on major psychiatric disorders, such as schizophrenia, major depressive disorder, bipolar disorder, attention-deficit/hyperactivity disorder, and addiction. Methodological challenges include: performing genetic analyses in small study populations used in imaging studies; inclusion of patients with psychiatric comorbidities; and the extensive variability across studies in neuroimaging protocols, neurobehavioral task probes, and analytic strategies. Moreover, few studies use pharmacogenetic designs that permit testing of genotype × drug effects. As a result of these limitations, few findings have been fully replicated. Future studies that pre-screen participants for genetic variants selected a priori based on drug metabolism and targets have the greatest potential to advance the science and practice of psychiatric treatment. PMID:23793356

In this review, we highlight the role of neuroimaging techniques in studying the emotional and cognitive-behavioral components of the addiction syndrome by focusing on the neural substrates subserving them. The phenomenology of drug addiction can be characterized by a recurrent pattern of subjective experiences that includes drug intoxication, craving, bingeing, and withdrawal with the cycle culminating in a persistent preoccupation with obtaining, consuming, and recovering from the drug. In the past two decades, imaging studies of drug addiction have demonstrated deficits in brain circuits related to reward and impulsivity. The current review focuses on studies employing positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and electroencephalography (EEG) to investigate these behaviors in drug-addicted human populations. We begin with a brief account of drug addiction followed by a technical account of each of these imaging modalities. We then discuss how these techniques have uniquely contributed to a deeper understanding of addictive behaviors.

In this review, we highlight the role of neuroimaging techniques in studying the emotional and cognitive-behavioral components of the addiction syndrome by focusing on the neural substrates subserving them. The phenomenology of drug addiction can be characterized by a recurrent pattern of subjective experiences that includes drug intoxication, craving, bingeing, and withdrawal with the cycle culminating in a persistent preoccupation with obtaining, consuming, and recovering from the drug. In the past two decades, imaging studies of drug addiction have demonstrated deficits in brain circuits related to reward and impulsivity. The current review focuses on studies employing positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and electroencephalography (EEG) to investigate these behaviors in drug-addicted human populations. We begin with a brief account of drug addiction followed by a technical account of each of these imaging modalities. We then discuss how these techniques have uniquely contributed to a deeper understanding of addictive behaviors. PMID:22117165

The neurobiological bases underlying the generation of auditory hallucinations, a distressing and paradigmatic symptom of schizophrenia, are still unknown in spite of in-depth phenomenological descriptions. This work aims to make a critical review of the latest published literature in recent years, focusing on functional neuroimagingstudies (PET, SPECT, fMRI) of auditory hallucinations. Thus, the studies are classified according to whether they are sensory activation, trait and state. The two main hypotheses proposed to explain the phenomenon, external speech vs. subvocal or inner speech, are also explained. Finally, the latest unitary theory as well as the limitations the studies published are commented on. The need to continue investigating in this field, that is still underdeveloped, is posed in order to understand better the etiopathogenesis of auditory hallucinations in schizophrenia.

This paper reviews research literature on cognitive load measurement in learning and neuroimaging, and describes a mapping between the main elements of cognitive load theory and findings in functional neuroanatomy. It is argued that these findings may lead to the improved measurement of cognitive load using neuroimaging. The paper describes how…

Neuroimaging techniques are becoming not only more and more sophisticated but are also coming to be increasingly accessible to researchers. One thing that one should take note of is the potential of neuroimaging research within second language acquisition (SLA) to contribute to issues pertaining to the plasticity of the adult brain and to general…

Increased circulating levels of liver enzymes emerging during treatment with psychotropic drugs are frequently encountered and, in general, attributed to drug metabolism or toxic effects. Because obesity was shown to be associated with elevated liver enzyme levels in different non-psychiatric study samples, we hypothesized that drug-induced weight gain might be an additional causative factor. We tested this hypothesis in 67 inpatients who received psychopharmacological treatment across five weeks. Stepwise linear regression was used to predict changes in the serum levels of aspartate-amino transferase (ASAT) and alanine-amino transferase (ALAT) by changes in the body mass index (BMI), by changes in other biological parameters related to body weight (tumor necrosis factor-alpha [TNF-alpha], soluble TNF receptors [sTNF-R], interleukin-6 [IL-6], leptin plasma levels) and by the respective liver enzyme baseline level. BMI changes from baseline to endpoint were significantly associated with the changes in ALAT and ASAT levels across five weeks of treatment and with ALAT and ASAT levels at the end point of the study. The baseline levels of ALAT and ASAT also had a significant impact on these liver enzyme level changes, whereas all other variables had not. These results suggest that weight gain-associated metabolic changes occurring during treatment with psychotropic drugs have consistent and clinically relevant effects on the liver.

Abstract Deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) represents a powerful clinical tool for the alleviation of many motor symptoms that are associated with Parkinson's disease. Despite its extensive use, the underlying therapeutic mechanisms of STN-DBS remain poorly understood. In the present review, we integrate and discuss recent literature examining the network effects of STN-DBS for Parkinson's disease, placing emphasis on neuroimaging findings, including functional magnetic resonance imaging, positron emission tomography, and single-photon emission computed tomography. These techniques enable the noninvasive detection of brain regions that are modulated by DBS on a whole-brain scale, representing a key experimental strength given the diffuse and far-reaching effects of electrical field stimulation. By examining these data in the context of multiple hypotheses of DBS action, generally developed through clinical and physiological observations, we define a multitude of consistencies and inconsistencies in the developing literature of this rapidly moving field. PMID:24147633

Neuroimagingstudies have verified the important integrative role of the basal ganglia during affective vocalizations. They, however, also point to additional regions supporting vocal monitoring, auditory-motor feedback processing, and online adjustments of vocal motor responses. For the case of affective vocalizations, we suggest partly extending the model to fully consider the link between primate-general and human-specific neural components.

This neuroimagingstudy examines the development of cognitive flexibility using the Change task in a sample of youths and adults. The Change task requires subjects to inhibit a prepotent response and substitute an alternative response, and the task incorporates an algorithm that adjusts task difficulty in response to subject performance. Data from…

In recent years, there has been an increasing interest in late-onset mental disorders. Among them, geriatric schizophrenia and bipolar disorder are significant health care risks and major causes of disability. We discussed whether late-onset schizophrenia (LOS) and late-onset bipolar (LOB) disorder can be a separate entity from early-onset schizophrenia (EOS) and early-onset bipolar (EOB) disorder in a subset of late-life schizophrenia or late-life bipolar disorder through neuroimagingstudies. A literature search for imaging studies of LOS or LOB was performed in the PubMed database. Search terms used were "(imaging OR MRI OR CT OR SPECT OR DTI OR PET OR fMRI) AND (schizophrenia or bipolar disorder) AND late onset." Articles that were published in English before October 2013 were included. There were a few neuroimagingstudies assessing whether LOS and LOB had different disease-specific neural substrates compared with EOS and EOB. These researches mainly observed volumetric differences in specific brain regions, white matter hyperintensities, diffusion tensor imaging, or functional neuroimaging to explore the differences between LOS and LOB and EOS and EOB. The aim of this review was to highlight the neural substrates involved in LOS and LOB through neuroimagingstudies. The exploration of neuroanatomical markers may be the key to the understanding of underlying neurobiology in LOS and LOB.

Childhood maltreatment is a stressor that can lead to the development of behavior problems and affect brain structure and function. This review summarizes the current evidence for the effects of childhood maltreatment on behavior, cognition and the brain in adults and children. Neuropsychological studies suggest an association between child abuse and deficits in IQ, memory, working memory, attention, response inhibition and emotion discrimination. Structural neuroimagingstudies provide evidence for deficits in brain volume, gray and white matter of several regions, most prominently the dorsolateral and ventromedial prefrontal cortex but also hippocampus, amygdala, and corpus callosum (CC). Diffusion tensor imaging (DTI) studies show evidence for deficits in structural interregional connectivity between these areas, suggesting neural network abnormalities. Functional imaging studies support this evidence by reporting atypical activation in the same brain regions during response inhibition, working memory, and emotion processing. There are, however, several limitations of the abuse research literature which are discussed, most prominently the lack of control for co-morbid psychiatric disorders, which make it difficult to disentangle which of the above effects are due to maltreatment, the associated psychiatric conditions or a combination or interaction between both. Overall, the better controlled studies that show a direct correlation between childhood abuse and brain measures suggest that the most prominent deficits associated with early childhood abuse are in the function and structure of lateral and ventromedial fronto-limbic brain areas and networks that mediate behavioral and affect control. Future, large scale multimodal neuroimagingstudies in medication-naïve subjects, however, are needed that control for psychiatric co-morbidities in order to elucidate the structural and functional brain sequelae that are associated with early environmental adversity

Concurrences of scientific, cultural, and economic developments in the past decade have changed psychiatric practice and psychiatric training. The explosion in neurobiological sciences has left residents with an overwhelming amount of neurobiology to master at the same time that managed care has led to a de-emphasis on psychiatrists providing psychotherapy. Consequently, many residents are left questioning the relevance of psychodynamics for psychiatry, given that the majority will function primarily as prescribers. However, the illusion, increasingly common in our culture, that medications are a simple fix leaves residents unprepared to make sense of the complex and irrational processes that happen in the acts of prescribing and taking medications (or not taking medications). Consequently, residents may feel confused, angry, hopeless, and/or abandoned in their role. These residents are often hungry for a context to explain why they feel hopeless, confused, or defeated in carrying out the "simple" task of prescribing. A psychodynamic understanding can provide such a holding context, just as it can give residents tools for backing out of futile and/or destructive enactments and turning conflicts around medications to some therapeutic good. Many psychodynamic concepts that initially may have seemed to residents part of some arcane and outmoded pseudoscience suddenly become relevant when they provide both a context for understanding the resident's distress and useful clinical tools. Those psychodynamic psychiatrists wishing to promulgate a psychodynamic understanding may need to meet psychiatric trainees at their developmental level and take seriously the current emphasis on providing effective somatic treatments. By engaging trainees at the junction of psychodynamics and psychopharmacology, psychodynamic psychiatrists may find a more receptive audience and open the door for greater interest in developing psychodynamic understanding and technical skills.

The following psychopharmacological effects of adrafinil have been observed in mice: increase in locomotor activity (64-256 mg.kg-1), antagonism (16-128 mg.kg-1) of the hypnotic effects of barbitone but not of pentobarbitone, reduction of immobility duration in the forced swimming test (16-256 mg.kg-1); slight antagonism (256 mg.kg-1) of electroshock-induced convulsions; no modification of rectal temperature; no stereotyped or climbing behaviour; no increase in lethality in aggregated mice (LD50 isolated = 1022 mg.kg-1, LD50 aggregated = 859 mg.kg-1); lack of effects on the provisional tests for antidepressants: no interaction with reserpine-, oxotremorine-, or apomorphine-induced hypothermia but potentiation of yohimbine-induced toxicity; lack of peripheral sympathetic effects (no mydriasis, no salivation, no contraction of the pilomotor muscles, no antagonism of reserpine-induced ptosis); lack of peripheral anticholinergic effects (no mydriasis, no antagonism of oxotremorine-induced salivation or lacrimation). As compared to no analeptic, anticholinergic or antidepressant drugs, adrafinil shows a unique behavioural profile in mice defined on the one hand by a specific stimulant activity associated with antidepressant-like effects that do no seem related to a beta-adrenergic mechanism and on the other hand by a lack of dopaminergic effects. Most adrafinil-induced effects (increase in locomotor activity, reduction of immobility duration in the forced swimming test) may correspond to a central alpha 1-adrenergic stimulation, but the unexpected lack of peripheral sympathetic effects remains unexplained.

This revision of previous algorithms for the pharmacotherapy of generalized anxiety disorder was developed by the Psychopharmacology Algorithm Project at the Harvard South Shore Program. Algorithms from 1999 and 2010 and associated references were reevaluated. Newer studies and reviews published from 2008-14 were obtained from PubMed and analyzed with a focus on their potential to justify changes in the recommendations. Exceptions to the main algorithm for special patient populations, such as women of childbearing potential, pregnant women, the elderly, and those with common medical and psychiatric comorbidities, were considered. Selective serotonin reuptake inhibitors (SSRIs) are still the basic first-line medication. Early alternatives include duloxetine, buspirone, hydroxyzine, pregabalin, or bupropion, in that order. If response is inadequate, then the second recommendation is to try a different SSRI. Additional alternatives now include benzodiazepines, venlafaxine, kava, and agomelatine. If the response to the second SSRI is unsatisfactory, then the recommendation is to try a serotonin-norepinephrine reuptake inhibitor (SNRI). Other alternatives to SSRIs and SNRIs for treatment-resistant or treatment-intolerant patients include tricyclic antidepressants, second-generation antipsychotics, and valproate. This revision of the GAD algorithm responds to issues raised by new treatments under development (such as pregabalin) and organizes the evidence systematically for practical clinical application.

The most outstanding novel of the Spanish literature, Don Quixote, represents the source to which the different specialists who intend to deepen their knowledge of the late Renaissance society usually address. This masterpiece of Miguel de Cervantes has been frequently approached from the psychopathological perspective to obtain a psychiatric diagnosis of its main character, Alonso Quijano. Also, other clinical approaches from the traumatological and general therapeutical view (oils, ointments, balms and other pharmacy preparations) have been frequent. We have tackled Don Quixote from the psychopharmacological perspective, a barely explored field. In this work, we intend to study the therapeutical cures used during the Cervantine time for the treatment of insane and mentally disturbed people (sedatives like opium, laxatives like hellebore, tonics, irritants and surgical techniques like bloodlettings and ) and we analyze the limited and unspecific therapies, mainly of herbal origin (balms, purgatives and emetics), which Cervantes reveals to us in his novel. Among them, rhubarb root (Rumex alpinus), seeds of spurge (Euphorbia lathyris), St. John's Wort (Hypericum perforatum), main ingredient of Aparicio's oil, and rosemary (Rosmarinus officinalis), primary component of the famous balsam of Fierabras, should be highlighted. We have also examined the possible scientific influences which might have inspired Cervantes in this field, mainly the works of Juan Huarte de San Juan The examination of men's wits and the one of Andres Laguna Dioscorides' materia medica.

The likelihood of being helped or harmed (LHH) ratio is an indirect measure of effect size. It tells the reader how much as likely a patient is to benefit from a treatment as to suffer from an adverse outcome with that treatment; larger values for LHH indicate more favorable treatment outcomes. The numerator for LHH is usually a measure of response or remission with a treatment, and the denominator is usually a measure of all-cause discontinuation or discontinuation due to adverse events; so, there can be more than 1 LHH statistic for a study. As an example, an LHH of 5 could indicate that after removal of placebo effects a patient is 5 times as likely to respond to a treatment as to drop out of treatment because of the experience of an adverse event. This article explains the LHH with the help of a worked example, shows how the LHH can be derived from the numbers needed to treat and harm (NNT, NNH) statistics, discusses practical issues related to the concept, and considers its limitations. The LHH is little used in clinical psychopharmacology, and authors who report or review clinical trial data should consider presenting all the LHH information that is clinically relevant in addition to NNT, NNH, and other information. Because LHH statistics present the results of risk-benefit trade-off analyses, they can help clinicians and patients more easily evaluate potential treatments during decision-making processes.

Developmental changes in the cardiovascular system could have an impact on risks associated with psychopharmacological interventions. Children may be more vulnerable to adverse cardiac events due to immaturity in autonomic control of the heart. These changes are incompletely understood and are characterized in this study. A consecutive series of 70 boys, aged 6-14 years, was recruited. Developmental variation in the autonomic nervous system was evaluated by assessing heart period variability (HPV), pulse, and blood pressure in response to orthostasis. Increased age correlated significantly with greater heart rate and diastolic blood pressure response to orthostasis. HPV at rest and in response to tilt did not significantly correlate with age. Boys with family histories of hypertension had a significantly greater blood pressure response to orthostasis. These findings suggest that developmental age-related changes in the sympathetic nervous system, as reflected by changes of pulse and blood pressure response to tilt, occur across this age range. Parasympathetic changes, as reflected by HPV, do not. In light of these findings, more research is needed on children's and adolescents' relative cardiac risk with psychotropic medications as opposed to adults'.

Seasonal affective disorder (SAD) is defined as a subtype of mood disorders in DSM 5, and it is characterized by a seasonal onset. SAD is proposed to be related to the seasonal changes in naturally occurring light, and the use of bright light therapy for depressive symptoms has been shown to reduce them in placebo controlled trials. Cognitive behavioral therapy has also been demonstrated to be effective in SAD. This review article aims to focus on the psychopharmacological treatment options for SAD. According to clinical trial results, first line treatment options seem to be sertraline and fluoxetine, and are well tolerated by the patients. There is some evidence that other antidepressants (e.g. bupropion) might be effective as well. Although clinical trials have shown that some of these antidepressants may be of benefit, a recent review has concluded that there is not enough evidence to support the use of any of these agents for the treatment of SAD yet. Moreover, more studies are still needed to evaluate the effectiveness of other treatment options, e.g., propranolol, melatonin, hypericum, etc. In addition to the above proposed treatments, patients with seasonal depressive symptoms should thoroughly be evaluated for any cues of bipolarity, and their treatment should be planned accordingly.

This review and meta-analysis aims at summarizing and integrating the human neuroimagingstudies that report periaqueductal gray (PAG) involvement; 250 original manuscripts on human neuroimaging of the PAG were identified. A narrative review and meta-analysis using activation likelihood estimates is included. Behaviors covered include pain and pain modulation, anxiety, bladder and bowel function and autonomic regulation. Methods include structural and functional magnetic resonance imaging, functional connectivity measures, diffusion weighted imaging and positron emission tomography. Human neuroimagingstudies in healthy and clinical populations largely confirm the animal literature indicating that the PAG is involved in homeostatic regulation of salient functions such as pain, anxiety and autonomic function. Methodological concerns in the current literature, including resolution constraints, imaging artifacts and imprecise neuroanatomical labeling are discussed, and future directions are proposed. A general conclusion is that PAG neuroimaging is a field with enormous potential to translate animal data onto human behaviors, but with some growing pains that can and need to be addressed in order to add to our understanding of the neurobiology of this key region. PMID:22197740

Conversion disorder (CD) is a syndrome of neurological symptoms arising without organic cause, arguably in response to emotional stress, but the exact neural substrates of these symptoms and the underlying mechanisms remain poorly understood with the hunt for a biological basis afoot for centuries. In the past 15 years, novel insights have been gained with the advent of functional neuroimagingstudies in patients suffering from CDs in both motor and nonmotor domains. This review summarizes recent functional neuroimagingstudies including functional magnetic resonance imaging (fMRI), single photon emission computerized tomography (SPECT), and positron emission tomography (PET) to see whether they bring us closer to understanding the etiology of CD. Convergent functional neuroimaging findings suggest alterations in brain circuits that could point to different mechanisms for manifesting functional neurological symptoms, in contrast with feigning or healthy controls. Abnormalities in emotion processing and in emotion-motor processing suggest a diathesis, while differential reactions to certain stressors implicate a specific response to trauma. No comprehensive theory emerges from these clues, and all results remain preliminary, but functional neuroimaging has at least given grounds for hope that a model for CD may soon be found. PMID:26834476

Conversion disorder (CD) is a syndrome of neurological symptoms arising without organic cause, arguably in response to emotional stress, but the exact neural substrates of these symptoms and the underlying mechanisms remain poorly understood with the hunt for a biological basis afoot for centuries. In the past 15 years, novel insights have been gained with the advent of functional neuroimagingstudies in patients suffering from CDs in both motor and nonmotor domains. This review summarizes recent functional neuroimagingstudies including functional magnetic resonance imaging (fMRI), single photon emission computerized tomography (SPECT), and positron emission tomography (PET) to see whether they bring us closer to understanding the etiology of CD. Convergent functional neuroimaging findings suggest alterations in brain circuits that could point to different mechanisms for manifesting functional neurological symptoms, in contrast with feigning or healthy controls. Abnormalities in emotion processing and in emotion-motor processing suggest a diathesis, while differential reactions to certain stressors implicate a specific response to trauma. No comprehensive theory emerges from these clues, and all results remain preliminary, but functional neuroimaging has at least given grounds for hope that a model for CD may soon be found.

Few parents of a teenager are surprised to hear that the brain of a 16-year-old is different from the brain of an 8-year-old. Yet to pin down these differences in a rigorous scientific way has been elusive. Magnetic resonance imaging, with the capacity to provide exquisitely accurate quantifications of brain anatomy and physiology without the use of ionizing radiation, has launched a new era of adolescent neuroscience. Longitudinal studies of subjects from ages 3-30 years demonstrate a general pattern of childhood peaks of gray matter followed by adolescent declines, functional and structural increases in connectivity and integrative processing, and a changing balance between limbic/subcortical and frontal lobe functions, extending well into young adulthood. Although overinterpretation and premature application of neuroimaging findings for diagnostic purposes remains a risk, converging data from multiple imaging modalities is beginning to elucidate the implications of these brain changes on cognition, emotion, and behavior.

The experience of art is a complex one. It emerges from the interaction of multiple cognitive and affective processes. Neuropsychological and neuroimagingstudies are revealing the broadly distributed network of brain regions upon which it relies. This network can be divided into three functional components: (i) prefrontal, parietal, and temporal cortical regions support evaluative judgment, attentional processing, and memory retrieval; (ii) the reward circuit, including cortical, subcortical regions, and some of its regulators, is involved in the generation of pleasurable feelings and emotions, and the valuation and anticipation of reward; and (iii) attentional modulation of activity in low-, mid-, and high-level cortical sensory regions enhances the perceptual processing of certain features, relations, locations, or objects. Understanding how these regions act in concert to produce unique and moving art experiences and determining the impact of personal and cultural meaning and context on this network the biological foundation of the experience of art--remain future challenges.

Positron emission tomography (PET) neuroimaging in nonhuman primates has led to significant advances in our current understanding of the neurobiology and treatment of stimulant addiction in humans. PET neuroimaging has defined the in vivo biodistribution and pharmacokinetics of abused drugs and related these findings to the time course of behavioral effects associated with their addictive properties. With novel radiotracers and enhanced resolution, PET neuroimaging techniques have also characterized in vivo drug interactions with specific protein targets in the brain, including neurotransmitter receptors and transporters. In vivo determinations of cerebral blood flow and metabolism have localized brain circuits implicated in the effects of abused drugs and drug-associated stimuli. Moreover, determinations of the predisposing factors to chronic drug use and long-term neurobiological consequences of chronic drug use, such as potential neurotoxicity, have led to novel insights regarding the pathology and treatment of drug addiction. However, similar approaches clearly need to be extended to drug classes other than stimulants. Although dopaminergic systems have been extensively studied, other neurotransmitter systems known to play a critical role in the pharmacological effects of abused drugs have been largely ignored in nonhuman primate PET neuroimaging. Finally, the study of brain activation with PET neuroimaging has been replaced in humans mostly by functional magnetic resonance imaging (fMRI). There has been some success in implementing pharmacological fMRI in awake nonhuman primates. Nevertheless, the unique versatility of PET imaging will continue to complement the systems-level strengths of fMRI, especially in the context of nonhuman primate drug abuse research.

Objective: For a variety of pedagogical, political and financial reasons, there are major problems in achieving effective teaching of cutting-edge psychopharmacology for psychiatric residents. This article focuses on ways to improve the teaching/learning process, in part through the use of structured curricula. The authors review 1) attempted…

This article discusses the evidence behind two approaches to psychopharmacological management in children with autism: selecting and treating target symptoms or treatment or curing the primary social impairment underlying autism. The effectiveness of stimulants, antidepressants, melatonin, naltrexone, fenfluramine, and secretin is appraised. The…

Objective: The authors describe a course of instruction for psychiatry residents that attempts to provide the cognitive and informational tools necessary to make scientifically grounded decision making a routine part of clinical practice. Methods: In weekly meetings over two academic years, the course covers the psychopharmacology of various…

Objective: To give academic researchers, government officials, and industry scientists an opportunity to assess the state of pediatric psychopharmacology and identify challenges facing professionals in the field. Method: Increased federal spending and the introduction of pediatric exclusivity led to large increases in pediatric psychopharmacology…

Counseling professionals and researchers have advocated for counselor training in psychopharmacology in order to heighten counselors' awareness of client needs and treatment standards (Ingersoll, 2000; King & Anderson, 2004; Smith & Garcia, 2003). There has been a lack of this training within counselor education graduate programs (Buelow, Hebert,…

Notes that biological interventions have been relatively neglected within field of school psychology in terms of its professional training, research agendas, and professional relationships with other specialties within psychology. Responds to previous articles in this special miniseries on psychopharmacology with children and adolescents, and…

OBJECTIVE: To describe and examine the role of the pharmaceutical industry in the teaching of psychopharmacology to residents and medical students and to make recommendations for changes in curriculum and policy based on these findings. METHODS: Literature reviews and discussions with experts, educators, and trainees. RESULTS: The pharmaceutical…

Reviews literature on pediatric psychopharmacology practice, lack of empirical support for efficacy and safety of most psychotropics for pediatric use, and need for further basic and clinical trials research and evaluation. Identifies shortcomings in training and experience that must be addressed if school psychology is to meet demands of three…

Psychopharmacology has had some bad publicity lately. Frankly, there have been some major problems along the way in developing new effective drugs for psychiatric disorders. After a prolonged period of high investments but low success rates, big pharmaceutical companies seem to retract their activities in the psychopharmacology field. Yet, the burden of mental disorders is likely to keep on growing in the next decades. In this position paper, we focus on drug development for depression and anxiety disorders, to narrow the scope of the assay. We describe the current situation of the psychopharmacology field, and analyse some of the methods and paradigms that have brought us here, but which should perhaps change to bring us even further. In addition, some of the factors contributing to the current stagnation in psychopharmacology are discussed. Finally, we suggest a number of changes that could lead to a more rational strategy for central nervous system drug development and which may circumvent some of the pitfalls leading to "me too" approaches. Central to the suggested changes, is the notion that mental disorders do not lead to several symptoms, but a network of causally related symptoms convolutes into a mental disorder. We call upon academia to put these changes in the early phases of drug development into effect.

Objective: To describe diagnostic and psychotropic medication prescription characteristics among college students referred by college counseling centers for psychopharmacologic evaluation. Participants: Participants were 540 college students referred by 6 college counseling centers in Massachusetts between November 2005 and May 2011. Methods:…

The present work's purpose is to open a discussion on the notion of Resistance in Psychopharmacology. Despite the fact that the phenomenon is observable in psychiatric practice, its meaning and consequences for medical practice are not sufficiently established, so that a critical reformulation is required for the sake of greater conceptual clarity in this area.

School psychologists frequently examine children who are prescribed psychotropic medications. With advanced training in psychological assessment and professional consultation, school psychologists may play an integral role in assisting with children's psychopharmacological treatment regimens. In this vein, this article discusses various ways for…

The article examines the World Health Organization's Model List of Essential Medicines (EML) and suggests modification for appropriate psychopharmacological treatment of child- and adolescent-onset mental disorders. The EML enlists few of the psychotropic medicines that are useful for the treatment of young people thereby limiting the…

Discusses the potential uses and abuses of psychopharmacologic therapy with children or adolescents who display learning, emotional, or behavioral disorders. Explores the indications and contraindications of such therapy and enumerates the known side effects of the most frequently prescribed medications, including psychostimulants,…

Background Melatonin (MLT) is a pleiotropic neurohormone controlling many physiological processes and whose dysfunction may contribute to several different diseases, such as neurodegenerative diseases, circadian and mood disorders, insomnia, type 2 diabetes and pain. Melatonin is synthesized by the pineal gland during the night and acts through 2 G-protein coupled receptors (GPCRs), MT1 (MEL1a) and MT2 (MEL1b). Although a bulk of research has examined the physiopathological effects of MLT, few studies have investigated the selective role played by MT1 and MT2 receptors. Here we have reviewed current knowledge about the implications of MT2 receptors in brain functions. Methods We searched PubMed, Web of Science, Scopus, Google Scholar and articles reference lists for studies on MT2 receptor ligands in sleep, anxiety, neuropsychiatric diseases and psychopharmacology, including genetic studies on the MTNR1B gene, which encodes the melatonin MT2 receptor. Results These studies demonstrate that MT2 receptors are involved in the pathophysiology and pharmacology of sleep disorders, anxiety, depression, Alzheimer disease and pain and that selective MT2 receptor agonists show hypnotic and anxiolytic properties. Limitations Studies examining the role of MT2 receptors in psychopharmacology are still limited. Conclusion The development of novel selective MT2 receptor ligands, together with further preclinical in vivo studies, may clarify the role of this receptor in brain function and psychopharmacology. The superfamily of GPCRs has proven to be among the most successful drug targets and, consequently, MT2 receptors have great potential for pioneer drug discovery in the treatment of mental diseases for which limited therapeutic targets are currently available. PMID:23971978

An individual's tendency to show exaggerated or otherwise dysregulated cardiovascular reactions to acute stressors has long been associated with increased risk for clinical and preclinical endpoints of coronary heart disease (CHD). However, the ‘brain-body’ pathways that link stressor-evoked cardiovascular reactions to CHD risk remain uncertain. This review summarizes emerging neuroimaging research indicating that individual differences in stressor-evoked blood pressure reactivity (a particular form of cardiovascular reactivity) are associated with activation patterns in corticolimbic brain areas that are jointly involved in processing stressors and regulating the cardiovascular system. As supported empirically by activation likelihood estimates derived from a meta-analysis, these corticolimbic areas include divisions of the cingulate cortex, insula, and amygdala—as well as networked cortical and subcortical areas involved in mobilizing hemodynamic and metabolic support for stress-related behavioral responding. Contextually, the research reviewed here illustrates how behavioral medicine and health neuroscience methods can be integrated to help characterize the ‘brain-body’ pathways that mechanistically link stressful experiences with CHD risk. PMID:19410652

Dementia is one of the most disabling conditions. Alzheimer's disease and vascular dementia (VaD) are the most frequent causes. Subcortical VaD is consequent to deep-brain small vessel disease (SVD) and is the most frequent form of VaD. Its pathological hallmarks are ischemic white matter changes and lacunar infarcts. Degenerative and vascular changes often coexist, but mechanisms of interaction are incompletely understood. The term mild cognitive impairment defines a transitional state between normal ageing and dementia. Pre-dementia stages of VaD are also acknowledged (vascular mild cognitive impairment, VMCI). Progression relates mostly to the subcortical VaD type, but determinants of such transition are unknown. Variability of phenotypic expression is not fully explained by severity grade of lesions, as depicted by conventional MRI that is not sensitive to microstructural and metabolic alterations. Advanced neuroimaging techniques seem able to achieve this. Beside hypoperfusion, blood-brain-barrier dysfunction has been also demonstrated in subcortical VaD. The aim of the Vascular Mild Cognitive Impairment Tuscany Study is to expand knowledge about determinants of transition from mild cognitive impairment to dementia in patients with cerebral SVD. This paper summarizes the main aims and methodological aspects of this multicenter, ongoing, observational study enrolling patients affected by VMCI with SVD. PMID:22550606

The current definition of mild traumatic brain injury (MTBI) is in flux. Presently, there are at least three working definitions of this disorder in the United States, with no clear consensus. Functional neuroimaging, such as single photon emission computed tomography (SPECT) and positron emission tomography (PET), initially showed promise in their ability to improve the diagnostic credibility of MTBI. Over the past decade, that promise has not been fulfilled and there is a paucity of quality studies or standards for the application of functional neuroimaging to traumatic brain injury, particularly in litigation. The legal profession is ahead of the science in this matter. The emergence of neurolaw is driving a growing use of functional neuroimaging, as a sole imaging modality, used by lawyers in an attempt to prove MTBI at trial. The medical literature on functional neuroimaging and its applications to MTBI is weak scientifically, sparse in quality publications, lacking in well-designed controlled studies, and currently does not meet the complete standards of Daubert v. Merrell Dow Pharmaceuticals, Inc., for introduction of scientific evidence at trial. At the present time, there is a clear lack of clinical correlation between functional neuroimaging of MTBI and behavioral, neuropsychological, or structural neuroimaging deficits. The use of SPECT or PET, without concurrent clinical correlation with structural neuroimaging (CT or MRI), is not recommended to be offered as evidence of MTBI in litigation.

A recent review of neuroimaging techniques indicates that new developments have primarily occurred in the area of data acquisition hardware/software technology. For example, new pulse sequences on standard clinical imagers and high-powered, rapidly oscillating magnetic field gradients used in echo planar imaging (EPI) have advanced MRI into the functional imaging arena. Significant developments in tomograph design have also been achieved for monitoring the distribution of positron-emitting radioactive tracers in the body (PET). Detector sizes, which pose a limit on spatial resolution, have become smaller (e.g., 3--5 mm wide) and a new emphasis on volumetric imaging has emerged which affords greater sensitivity for determining locations of positron annihilations and permits smaller doses to be utilized. Electromagnetic techniques have also witnessed growth in the ability to acquire data from the whole head simultaneously. EEG techniques have increased their electrode coverage (e.g., 128 channels rather than 16 or 32) and new whole-head systems are now in use for MEG. But the real challenge now is in the design and implementation of more sophisticated analyses to effectively handle the tremendous amount of physiological/anatomical data that can be acquired. Furthermore, such analyses will be necessary for integrating data across techniques in order to provide a truly comprehensive understanding of the functional organization of the human brain.

Tourette Syndrome (ts) is a developmental neuropsychiatric disorder of the central nervous system defined by the presence of chronic tics. While investigations of the underlying brain mechanisms have provided valuable information, a complete understanding of the pathophysiology of ts remains elusive. Neuroimaging methods provide remarkable tools for examining the human brain, and have been used to study brain structure and function in ts. In this article, we review ts neuroimagingstudies published in 2014–2015. We highlight a number of noteworthy studies due to their innovative methods and interesting findings. Yet, we note that many of the recent studies share common concerns, specifically susceptibility to motion artifacts and modest sample sizes. Thus, we encourage future work to carefully address potential methodological confounds and to study larger samples to increase the potential for replicable results. PMID:26543796

The extract of the nut of Tetracarpidium conophorum (TC), commonly known as African walnut, is widely used to relieve pain, increase sperm count, enhance sexual performance in males and as a nerve tonic in ethnomedicine. This study describes the psychopharmacological properties of the aqueous extract of the nut of TC in mice. The spectrum of activities studied were the effects of TC on the duration of immobility in the forced swim test of the behavioural despair model of depression; prolongation of the duration of sleep produced by thiopentone; amphetamine-induced stereotyped behaviour; and on pain episodes produced by acetic acid and by formalin. Orally administered TC (50-200 mg/kg) produced a significant and dose-related decrease in the duration of immobility in the forced swim test in mice. TC also exhibited analgesic property, as shown by its ability to reduce the frequency of abdominal constrictions induced by acetic acid and to inhibit the nociceptive responses produced by formalin. However, at the tested oral doses of 50-200 mg/kg, TC did not prolong the duration of sleep produced by thiopentone nor alter the pattern of the stereotyped behaviour induced by amphetamine. This investigation provides evidence that may support the ethnomedicinal applications of the extract of the nut of TC in the treatment of pain. The study also revealed that TC seems to demonstrate antidepressant-like activity, as evidenced by its ability to shorten the period of immobility in the forced swim test; however, further studies are necessary to clearly define the role of TC in depression.

Neurosurgical treatment of psychiatric disorders has been influenced by evolving neurobiological models of symptom generation. The advent of functional neuroimaging and advances in the neurosciences have revolutionized understanding of the functional neuroanatomy of psychiatric disorders. This article reviews neuroimagingstudies of depression from the last 3 decades and describes an emerging neurocircuitry model of mood disorders, focusing on critical circuits of cognition and emotion, particularly those networks involved in the regulation of evaluative, expressive and experiential aspects of emotion. The relevance of this model for neurotherapeutics is discussed, as well as the role of functional neuroimaging of psychiatric disorders.

Background Essential tremor is regarded to be a disease of the central nervous system. Neuroimaging is a rapidly growing field with potential benefits to both diagnostics and research. The exact role of imaging techniques with respect to essential tremor in research and clinical practice is not clear. A systematic review of the different imaging techniques in essential tremor is lacking in the literature. Methods We performed a systematic literature search combining the terms essential tremor and familial tremor with the following keywords: imaging, MRI, VBM, DWI, fMRI, PET and SPECT, both in abbreviated form as well as in full form. We summarize and discuss the quality and the external validity of each study and place the results in the context of existing knowledge regarding the pathophysiology of essential tremor. Results A total of 48 neuroimagingstudies met our search criteria, roughly divided into 19 structural and 29 functional and metabolic studies. The quality of the studies varied, especially concerning inclusion criteria. Functional imaging studies indicated cerebellar hyperactivity during rest and during tremor. The studies also pointed to the involvement of the thalamus, the inferior olive and the red nucleus. Structural studies showed less consistent results. Discussion and conclusion Neuroimaging techniques in essential tremor give insight into the pathophysiology of essential tremor indicating the involvement of the cerebellum as the most consistent finding. GABAergic dysfunction might be a major premise in the pathophysiological hypotheses. Inconsistencies between studies can be partly explained by the inclusion of heterogeneous patient groups. Improvement of scientific research requires more stringent inclusion criteria and application of advanced analysis techniques. Also, the use of multimodal neuroimaging techniques is a promising development in movement disorders research. Currently, the role of imaging techniques in essential tremor in daily

Serotonin (5-HT) release is the primary pharmacological mechanism of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') action in the primate brain. Dopamine release and direct stimulation of dopamine D2 and serotonin 5-HT2A receptors also contributes to the overall action of MDMA. The role of 5-HT1A receptors in the human psychopharmacology of MDMA, however, has not yet been elucidated. In order to reveal the consequences of manipulation at the 5-HT1A receptor system on cognitive and subjective effects of MDMA, a receptor blocking study using the mixed beta-adrenoreceptor blocker/5-HT1A antagonist pindolol was performed. Using a double-blind, placebo-controlled within-subject design, 15 healthy male subjects were examined under placebo (PL), 20 mg pindolol (PIN), MDMA (1.6 mg/kg b.wt.), MDMA following pre-treatment with pindolol (PIN-MDMA). Tasks from the Cambridge Neuropsychological Test Automated Battery were used for the assessment of cognitive performance. Psychometric questionnaires were applied to measure effects of treatment on core dimensions of Altered States of Consciousness, mood and state anxiety. Compared with PL, MDMA significantly impaired sustained attention and visual-spatial memory, but did not affect executive functions. Pre-treatment with PIN did not significantly alter MDMA-induced impairment of cognitive performance and only exerted a minor modulating effect on two psychometric scales affected by MDMA treatment ('positive derealization' and 'dreaminess'). Our findings suggest that MDMA differentially affects higher cognitive functions, but does not support the hypothesis from animal studies, that some of the MDMA effects are causally mediated through action at the 5-HT1A receptor system.

Magnetoencephalography (MEG) is a multi-channel, functional imaging technique. It measures the magnetic field produced by the primary electric currents inside the brain via a sensor array composed of a large number of superconducting quantum interference devices. The measurements are then used to estimate the locations, strengths, and orientations of these electric currents. This magnetic source imaging technique encompasses a great variety of signal processing and modeling techniques which include Inverse problem, MUltiple SIgnal Classification (MUSIC), Beamforming (BF), and Independent Component Analysis (ICA) method. A key problem with Inverse problem, MUSIC and ICA methods is that the number of sources must be detected a priori. Although BF method scans the source space on a point-to-point basis, the selection of peaks as sources, however, is finally made by subjective thresholding. In practice expert data analysts often select results based on physiological plausibility. This paper presents an eigenstructure approach for the source number detection in MEG neuroimaging. By sorting eigenvalues of the estimated covariance matrix of the acquired MEG data, the measured data space is partitioned into the signal and noise subspaces. The partition is implemented by utilizing information theoretic criteria. The order of the signal subspace gives an estimate of the number of sources. The approach does not refer to any model or hypothesis, hence, is an entirely data-led operation. It possesses clear physical interpretation and efficient computation procedure. The theoretical derivation of this method and the results obtained by using the real MEG data are included to demonstrates their agreement and the promise of the proposed approach.

Since the sample size of a typical neuroimagingstudy lacks sufficient statistical power to explore unknown genomic associations with brain phenotypes, several international genetic imaging consortia have been organized in recent years to pool data across sites. The challenges and achievements of these consortia are considered here with the goal of leveraging these resources to study addiction. The authors of this review have joined together to form an Addiction working group within the framework of the ENIGMA project, a meta-analytic approach to multisite genetic imaging data. Collectively, the Addiction working group possesses neuroimaging and genomic data obtained from over 10,000 subjects. The deadline for contributing data to the first round of analyses occurred at the beginning of May 2015. The studies performed on this data should significantly impact our understanding of the genetic and neurobiological basis of addiction.

This new algorithm for the pharmacotherapy of acute mania was developed by the Psychopharmacology Algorithm Project at the Harvard South Shore Program. The authors conducted a literature search in PubMed and reviewed key studies, other algorithms and guidelines, and their references. Treatments were prioritized considering three main considerations: (1) effectiveness in treating the current episode, (2) preventing potential relapses to depression, and (3) minimizing side effects over the short and long term. The algorithm presupposes that clinicians have made an accurate diagnosis, decided how to manage contributing medical causes (including substance misuse), discontinued antidepressants, and considered the patient's childbearing potential. We propose different algorithms for mixed and nonmixed mania. Patients with mixed mania may be treated first with a second-generation antipsychotic, of which the first choice is quetiapine because of its greater efficacy for depressive symptoms and episodes in bipolar disorder. Valproate and then either lithium or carbamazepine may be added. For nonmixed mania, lithium is the first-line recommendation. A second-generation antipsychotic can be added. Again, quetiapine is favored, but if quetiapine is unacceptable, risperidone is the next choice. Olanzapine is not considered a first-line treatment due to its long-term side effects, but it could be second-line. If the patient, whether mixed or nonmixed, is still refractory to the above medications, then depending on what has already been tried, consider carbamazepine, haloperidol, olanzapine, risperidone, and valproate first tier; aripiprazole, asenapine, and ziprasidone second tier; and clozapine third tier (because of its weaker evidence base and greater side effects). Electroconvulsive therapy may be considered at any point in the algorithm if the patient has a history of positive response or is intolerant of medications.

Data on medical treatment of children and adolescents with tic disorders are scarce. This study examined the administrative prevalence of psychopharmacological prescriptions in this patient group in Germany. Data of the largest German health insurance fund were analysed. In outpatients aged 0-19 years with diagnosed tic disorder, psychotropic prescriptions were evaluated for the years 2006 and 2011. In 2011, the percentage of psychotropic prescriptions was slightly higher than in 2006 (21.2 vs. 18.6%). The highest prescription prevalence was found in Tourette syndrome (51.5 and 53.0%, respectively). ADHD drugs were most frequently prescribed, followed by antipsychotics. In 2011, prescriptions of second generation antipsychotics (SGA) were higher and prescriptions of first generation antipsychotics (FGA) lower than in 2006. Concerning prescribed antipsychotic substances, in 2011 risperidone prescriptions were higher and tiapride prescriptions lower. Paediatricians issued 37.4%, and child and adolescent psychiatrists issued 37.1% of psychotropic prescriptions. The FGA/SGA ratio was highest in GPs (1.25) and lowest in child and adolescent psychiatrists (0.96). From 2006 to 2011, there was only a slight increase in psychotropic prescriptions for children and adolescents with a diagnosis of tic disorder in Germany, which stands in contrast towards the significant increase in psychotropic prescriptions in other child and adolescent psychiatric disorders (e.g. ADHD). There were marked differences in treatment patterns by tic disorder subgroups, with Tourette syndrome patients receiving most frequently psychopharmacotherapy. Risperidone prescriptions increased, probably reflecting a switch in prescribing practice towards up-to-date treatment guidelines. In primary care physicians, dissemination of current tic disorder treatment guidelines might constitute an important educational goal.

Human deep sleep is characterized by reduced sensory activity, responsiveness to stimuli, and conscious awareness. Given its ubiquity and reversible nature, it represents an attractive paradigm to study the neural changes which accompany the loss of consciousness in humans. In particular, the deepest stages of sleep can serve as an empirical test for the predictions of theoretical models relating the phenomenology of consciousness with underlying neural activity. A relatively recent shift of attention from the analysis of evoked responses toward spontaneous (or "resting state") activity has taken place in the neuroimaging community, together with the development of tools suitable to study distributed functional interactions. In this review we focus on recent functional Magnetic Resonance Imaging (fMRI) studies of spontaneous activity during sleep and their relationship with theoretical models for human consciousness generation, considering the global workspace theory, the information integration theory, and the dynamical core hypothesis. We discuss the venues of research opened by these results, emphasizing the need to extend the analytic methodology in order to obtain a dynamical picture of how functional interactions change over time and how their evolution is modulated during different conscious states. Finally, we discuss the need to experimentally establish absent or reduced conscious content, even when studying the deepest sleep stages.

Human deep sleep is characterized by reduced sensory activity, responsiveness to stimuli, and conscious awareness. Given its ubiquity and reversible nature, it represents an attractive paradigm to study the neural changes which accompany the loss of consciousness in humans. In particular, the deepest stages of sleep can serve as an empirical test for the predictions of theoretical models relating the phenomenology of consciousness with underlying neural activity. A relatively recent shift of attention from the analysis of evoked responses toward spontaneous (or “resting state”) activity has taken place in the neuroimaging community, together with the development of tools suitable to study distributed functional interactions. In this review we focus on recent functional Magnetic Resonance Imaging (fMRI) studies of spontaneous activity during sleep and their relationship with theoretical models for human consciousness generation, considering the global workspace theory, the information integration theory, and the dynamical core hypothesis. We discuss the venues of research opened by these results, emphasizing the need to extend the analytic methodology in order to obtain a dynamical picture of how functional interactions change over time and how their evolution is modulated during different conscious states. Finally, we discuss the need to experimentally establish absent or reduced conscious content, even when studying the deepest sleep stages. PMID:23717291

Dream is a state of consciousness characterized by internally-generated sensory, cognitive and emotional experiences occurring during sleep. Dream reports tend to be particularly abundant, with complex, emotional, and perceptually vivid experiences after awakenings from rapid eye movement (REM) sleep. This is why our current knowledge of the cerebral correlates of dreaming, mainly derives from studies of REM sleep. Neuroimaging results show that REM sleep is characterized by a specific pattern of regional brain activity. We demonstrate that this heterogeneous distribution of brain activity during sleep explains many typical features in dreams. Reciprocally, specific dream characteristics suggest the activation of selective brain regions during sleep. Such an integration of neuroimaging data of human sleep, mental imagery, and the content of dreams is critical for current models of dreaming; it also provides neurobiological support for an implication of sleep and dreaming in some important functions such as emotional regulation.

Although cannabis use disorder is strongly related to schizophrenia and treatment of patients with double diagnosis provides serious problem, specific pharmacological, molecular and therapeutical data on this subgroup are poorly available. In this paper we present a critical review on psychopharmacological boundaries of schizophrenia with concurrent cannabis use. The relevant data available in the literature suggest that a weaker compliance, poorer therapy response and higher sensitivity for extrapyramidal side effects are key features of schizophrenia and comorbid cannabis use disorder and represent a clinical challenge. Because of paucity of available research in the field there is not enough evidence to clearly depict the exact psychopharmacological profile of cannabis related schizophrenia. Further investigations are needed to assess phenotypic characteristics of this entity and to tailor effective treatment options accordingly.

Nowadays, the term receptor is obvious in psychopharmacology. However, this was not so obvious a century ago. To try to explain how drugs act, European scientists began to develop theories that turned into deeds with the scientific progress. Thus, the receptor concept and their applications in medicine and psychiatry began to gain substance. In this paper we relate the facts that have led to the current knowledge of receptor, the cornerstone of pharmacology.

The last two decades have witnessed the explosive growth in the development and use of noninvasive neuroimaging technologies that advance the research on human brain under normal and pathological conditions. Multimodal neuroimaging has become a major driver of current neuroimaging research due to the recognition of the clinical benefits of multimodal data, and the better access to hybrid devices. Multimodal neuroimaging computing is very challenging, and requires sophisticated computing to address the variations in spatiotemporal resolution and merge the biophysical/biochemical information. We review the current workflows and methods for multimodal neuroimaging computing, and also demonstrate how to conduct research using the established neuroimaging computing packages and platforms.

The last two decades have witnessed the explosive growth in the development and use of noninvasive neuroimaging technologies that advance the research on human brain under normal and pathological conditions. Multimodal neuroimaging has become a major driver of current neuroimaging research due to the recognition of the clinical benefits of multimodal data, and the better access to hybrid devices. Multimodal neuroimaging computing is very challenging, and requires sophisticated computing to address the variations in spatiotemporal resolution and merge the biophysical/biochemical information. We review the current workflows and methods for multimodal neuroimaging computing, and also demonstrate how to conduct research using the established neuroimaging computing packages and platforms.

Key methodological issues for designing, analyzing, and interpreting neuroimaging experiments are presented from the perspective of the framework of Coordination Dynamics. To this end, a brief overview of Coordination Dynamics is introduced, including the main concepts of control parameters and collective variables, theoretical modeling, novel experimental paradigms, and cardinal empirical findings. Basic conceptual and methodological issues for the design and implementation of coordination experiments in the context of neuroimaging are discussed. The paper concludes with a presentation of neuroimaging findings central to understanding the neural basis of coordination and addresses their relevance for the sport sciences. The latter include but are not restricted to learning and practice-related issues, the role of mental imagery, and the recovery of function following brain injury. PMID:18602998

The discipline of psychiatry appears poised at the edge of a paradigm shift. Enthusiasm about psychopharmacological treatments and neuroscientific understandings is giving way to a sobering recognition of the limitations of current biologically oriented approaches. Psychiatry training programs have both an opportunity and a responsibility to address the challenges presented by the evidence. Although the average psychiatrist would profess a biopsychosocial ideal, an examination of our practice, journals, and training curricula suggests that we still have a long way to go before we employ a truly integrated model. There is a compelling, though oft-neglected evidence base demonstrating that pharmacologic treatment outcomes are as dependent on psychological and interpersonal factors as on medical ones. In order to maximize our usefulness to patients, psychiatry must embrace more complex and integrated understandings, transcending reductionistic models that promote mind-body splits. This article explores some of the costs of a model that places disproportionate emphasis on a biological framework. Relevant evidence bases are reviewed that demonstrate the utility of emphasizing the psychology of psychopharmacology. Implications for psychiatric training are considered, and suggestions are made for better integrating meaning factors into psychopharmacology education.

Background Functional neuroimaging is being used in clinical psychiatry today despite the vigorous objections of many in the research community over issues of readiness. To date, a systematic examination of the perspectives of key stakeholders involved in this debate has not yet been attempted. To this fill this gap, we interviewed investigators who conduct functional neuroimagingstudies involving adults with mood disorders, schizophrenia, obsessive compulsive disorder, and/or attention deficit hyperactivity disorder, providers who offer clinical neuroimaging services in the open marketplace, and consumers of these services, in order to understand perspectives underlying different views and practices. Methods Semi-structured interviews were conducted over the telephone. Verbal consent was obtained and all interviews were audio recorded. Interviews of investigators and service providers followed the same interview guide. A separate set of questions was developed for consumers. All interviews were transcribed and made software ready. We applied the qualitative methodology of constant comparison to analyze the data, whereby two researchers independently analyzed the results into textual themes. Coding discrepancies were discussed until consensus was achieved. Results Investigators, service providers, and consumers held many common perspectives about the potential or actual risks and benefits of functional neuroimaging for mental illness. However, we also found striking divergences. Service providers focused on the challenges posed by the persistence of symptoms based diagnostic categories, whereas the limitations of the science in this area was the challenge noted most frequently by investigators. The majority of consumers stated that their expectations were met. Conclusion Our findings point toward a fundamental tension between academic investigators on the one hand, and commercial service providers and their customers on the other. This scenario poses dangers to

The continuity of the mind is suggested to mean the continuous spatiotemporal dynamics arising from the electrochemical signature of the neocortex: (i) globally through volume transmission in the gray matter as fields of neural activity, and (ii) locally through extrasynaptic signaling between fine distal dendrites of cortical neurons. If the continuity of dynamical systems across spatiotemporal scales defines a stream of consciousness then intentional metarepresentations as templates of dynamic continuity allow qualia to be semantically mapped during neuroimaging of specific cognitive tasks. When interfaced with a computer, such model-based neuroimaging requiring new mathematics of the brain will begin to decipher higher cognitive operations not possible with existing brain-machine interfaces.

Only a tiny fraction of the data and metadata produced by an fMRI study is finally conveyed to the community. This lack of transparency not only hinders the reproducibility of neuroimaging results but also impairs future meta-analyses. In this work we introduce NIDM-Results, a format specification providing a machine-readable description of neuroimaging statistical results along with key image data summarising the experiment. NIDM-Results provides a unified representation of mass univariate analyses including a level of detail consistent with available best practices. This standardized representation allows authors to relay methods and results in a platform-independent regularized format that is not tied to a particular neuroimaging software package. Tools are available to export NIDM-Result graphs and associated files from the widely used SPM and FSL software packages, and the NeuroVault repository can import NIDM-Results archives. The specification is publically available at: http://nidm.nidash.org/specs/nidm-results.html. PMID:27922621

Only a tiny fraction of the data and metadata produced by an fMRI study is finally conveyed to the community. This lack of transparency not only hinders the reproducibility of neuroimaging results but also impairs future meta-analyses. In this work we introduce NIDM-Results, a format specification providing a machine-readable description of neuroimaging statistical results along with key image data summarising the experiment. NIDM-Results provides a unified representation of mass univariate analyses including a level of detail consistent with available best practices. This standardized representation allows authors to relay methods and results in a platform-independent regularized format that is not tied to a particular neuroimaging software package. Tools are available to export NIDM-Result graphs and associated files from the widely used SPM and FSL software packages, and the NeuroVault repository can import NIDM-Results archives. The specification is publically available at: http://nidm.nidash.org/specs/nidm-results.html.

Noninvasive functional neuroimaging, as an important tool for basic neuroscience research and clinical diagnosis, continues to face the need of improving the spatial and temporal resolution. While existing neuroimaging modalities might approach their limits in imaging capability mostly due to fundamental as well as technical reasons, it becomes increasingly attractive to integrate multiple complementary modalities in an attempt to significantly enhance the spatiotemporal resolution that cannot be achieved by any modality individually. Electrophysiological and hemodynamic/metabolic signals reflect distinct but closely coupled aspects of the underlying neural activity. Combining fMRI and EEG/MEG data allows us to study brain function from different perspectives. In this review, we start with an overview of the physiological origins of EEG/MEG and fMRI, as well as their fundamental biophysics and imaging principles, we proceed with a review of the major advances in the understanding and modeling of neurovascular coupling and in the methodologies for the fMRI-EEG/MEG simultaneous recording. Finally, we summarize important remaining issues and perspectives concerning multimodal functional neuroimaging, including brain connectivity imaging.

PURPOSE To determine the yield of emergent neuroimaging among children with new-onset seizures presenting with status epilepticus. METHOD We performed a cross-sectional study of children seen at a single ED between 1995–2012 with new-onset seizure presenting with status epilepticus. We defined status epilepticus as a single seizure or multiple seizures without regaining consciousness lasting 30 minutes or longer. Our primary outcome was urgent or emergent intracranial pathology identified on neuroimaging. We categorized neuroimaging results as emergent if they would have changed acute management as assessed by a blinded neuroradiologist and neurologist. To ensure abnormalities were not missed, we review neuroimaging results for 30 days following the initial episode of SE. RESULTS We included 177 children presenting with new-onset seizure with status epilepticus, of whom 170 (96%) had neuroimaging performed. Abnormal findings were identified on neuroimaging in 64/177 (36%, 95% confidence interval 29–43%) children with 15 (8.5%, 95% confidence interval 5.2–14%) children having urgent or emergent pathology. Four (27%) of the 15 children with urgent or emergent findings had a normal non-contrast computed tomography scan and a subsequently abnormal magnetic resonance image. Longer seizure duration and older age were associated with urgent or emergent intracranial pathology. CONCLUSION A substantial minority of children with new-onset seizures presenting with status epilepticus have urgent or emergent intracranial pathology identified on neuroimaging. Clinicians should strongly consider emergent neuroimaging in these children. Magnetic resonance imaging is the preferred imaging modality when available and safe. PMID:26773658

While technological advancements in neuroimaging scanner engineering have improved the efficiency of data acquisition, electronic data capture methods will likewise significantly expedite the populating of large-scale neuroimaging databases. As they do and these archives grow in size, a particular challenge lies in examining and interacting with the information that these resources contain through the development of compelling, user-driven approaches for data exploration and mining. In this article, we introduce the informatics visualization for neuroimaging (INVIZIAN) framework for the graphical rendering of, and dynamic interaction with the contents of large-scale neuroimaging data sets. We describe the rationale behind INVIZIAN, detail its development, and demonstrate its usage in examining a collection of over 900 T1-anatomical magnetic resonance imaging (MRI) image volumes from across a diverse set of clinical neuroimagingstudies drawn from a leading neuroimaging database. Using a collection of cortical surface metrics and means for examining brain similarity, INVIZIAN graphically displays brain surfaces as points in a coordinate space and enables classification of clusters of neuroanatomically similar MRI images and data mining. As an initial step toward addressing the need for such user-friendly tools, INVIZIAN provides a highly unique means to interact with large quantities of electronic brain imaging archives in ways suitable for hypothesis generation and data mining.

While technological advancements in neuroimaging scanner engineering have improved the efficiency of data acquisition, electronic data capture methods will likewise significantly expedite the populating of large-scale neuroimaging databases. As they do and these archives grow in size, a particular challenge lies in examining and interacting with the information that these resources contain through the development of compelling, user-driven approaches for data exploration and mining. In this article, we introduce the informatics visualization for neuroimaging (INVIZIAN) framework for the graphical rendering of, and dynamic interaction with the contents of large-scale neuroimaging data sets. We describe the rationale behind INVIZIAN, detail its development, and demonstrate its usage in examining a collection of over 900 T1-anatomical magnetic resonance imaging (MRI) image volumes from across a diverse set of clinical neuroimagingstudies drawn from a leading neuroimaging database. Using a collection of cortical surface metrics and means for examining brain similarity, INVIZIAN graphically displays brain surfaces as points in a coordinate space and enables classification of clusters of neuroanatomically similar MRI images and data mining. As an initial step toward addressing the need for such user-friendly tools, INVIZIAN provides a highly unique means to interact with large quantities of electronic brain imaging archives in ways suitable for hypothesis generation and data mining. PMID:22536181

Neuroimaging markers have been widely used to predict the cognitive functions relevant to the progression of Alzheimer's disease (AD). Most previous studies identify the imaging markers without considering the brain structural correlations between neuroimaging measures. However, many neuroimaging markers interrelate and work together to reveal the cognitive functions, such that these relevant markers should be selected together as the phenotypic markers. To solve this problem, in this paper, we propose a novel network constrained feature selection (NCFS) model to identify the neuroimaging markers guided by the structural brain network, which is constructed by the sparse representation method such that the interrelations between neuroimaging features are encoded into probabilities. Our new methods are evaluated by the MRI and AV45-PET data from ADNI-GO and ADNI-2 (Alzheimer's Disease Neuroimaging Initiative). In all cognitive function prediction tasks, our new NCFS method outperforms other state-of-the-art regression approaches. Meanwhile, we show that the new method can select the correlated imaging markers, which are ignored by the competing approaches.

From an observer's perspective, pain is a fairly nebulous concept—it is not externally visible, its cause is not obvious, and perceptions of its intensity are mainly subjective. If difficulties in understanding the source and degree of pain are troublesome in contexts requiring social empathy, they are especially problematic in the legal setting. Tort law applies to both acute and chronic pain cases, but the lack of objective measures demands high thresholds of proof. However, recent developments in pain neuroimaging may clarify some of these inherent uncertainties, as studies purport detection of pain on an individual level. In analyzing the scientific and legal barriers of utilizing pain neuroimaging in court, it is prudent to discuss neuroimaging for deception, a topic that has garnered significant controversy due to premature attempts at introduction in the courtroom. Through comparing and contrasting the two applications of neuroimaging to the legal setting, this paper argues that the nature of tort law, the distinct features of pain, and the reduced vulnerability to countermeasures distinguish pain neuroimaging in a promising way. This paper further contends that the mistakes and lessons involving deception detection are essential to consider for pain neuroimaging to have a meaningful future in court. PMID:27774191

Interacting parenting thoughts and behaviors, supported by key brain circuits, critically shape human infants' current and future behavior. Indeed, the parent-infant relationship provides infants with their first social environment, forming templates for what they can expect from others, how to interact with them and ultimately how they go on to themselves to be parents. This review concentrates on magnetic resonance imaging experiments of the human parent brain, which link brain physiology with parental thoughts and behaviors. After reviewing brain imaging techniques, certain social cognitive and affective concepts are reviewed, including empathy and trust-likely critical to parenting. Following that is a thorough study-by-study review of the state-of-the-art with respect to human neuroimagingstudies of the parental brain-from parent brain responses to salient infant stimuli, including emotionally charged baby cries and brief visual stimuli to the latest structural brain studies. Taken together, this research suggests that networks of highly conserved hypothalamic-midbrain-limbic-paralimbic-cortical circuits act in concert to support parental brain responses to infants, including circuits for limbic emotion response and regulation. Thus, a model is presented in which infant stimuli activate sensory analysis brain regions, affect corticolimbic limbic circuits that regulate emotional response, motivation and reward related to their infant, ultimately organizing parenting impulses, thoughts and emotions into coordinated behaviors as a map for future studies. Finally, future directions towards integrated understanding of the brain basis of human parenting are outlined with profound implications for understanding and contributing to long term parent and infant mental health.

Given the important role of the dopamine transporter (DAT) in the addictive properties of cocaine, the development and use of compounds that target the DAT represents a reasonable approach for the pharmacological treatment of cocaine abuse. The present report describes a series of studies conducted in nonhuman primates that evaluated the effectiveness of DAT inhibitors in reducing cocaine self-administration. In addition, drug substitution studies evaluated the abuse liability of the DAT inhibitors. PET neuroimagingstudies quantified DAT occupancy at behaviorally relevant doses, characterized the time-course of drug uptake in brain, and documented drug-induced changes in cerebral blood flow as a model of brain activation. Selective DAT inhibitors were effective in reducing cocaine use but high (>70%) levels of DAT occupancy were associated with significant reductions in cocaine self-administration. The selective DAT inhibitors were reliably self-administered but rates of responding were lower than those maintained by cocaine even at higher levels of DAT occupancy. A profile of slow rate of drug uptake in brain accompanied by a gradual increase in extracellular dopamine may account for the more limited reinforcing effectiveness of the DAT inhibitors. Selective serotonin transporter (SERT) inhibitors were also effective in reducing cocaine use and blocked cocaine-induced brain activation and increases in extracellular dopamine. Co-administration of SERT inhibitors with a selective DAT inhibitor was more effective than the DAT inhibitor administered alone, even at comparable levels of DAT occupancy. The results indicate that combined inhibition of DAT and SERT may be a viable approach to treat cocaine addiction. PMID:19086766

Autism is an early developmental disorder. It leads to severe and durable disturbances. Given this problem, no treatment can be excluded a priori. Thus, many approaches are used to deal with autistic disorders. In France, pharmacological treatments are, for instance, largely and mostly used in adults. In the USA, these treatments concern 50% of persons with autism of any age. Nevertheless, they are rarely based on controlled studies. At the present, however, prescriptions and expected effects appear to be hard to localize. Furthermore, only few controlled studies validate their use. Aim - We offer a review of studies about medical treatments used in adolescents and adults with autism. They are classified in 3 categories: the first (category I) includes drugs used for their neurochemical effects focusing on autistic signs. The second (category II) covers drugs used for treatment of behavioural disorders frequently associated with autism. The third (category III) corresponds to a wide range of drugs or vitamins for wich only few case studies exist reporting irregular positive effects. The main hypothesis of this review is that autism involves a dysfunction of the neuromediation systems. This hypothesis opens new perspectives in the research of medical treatments in autism by focusing on molecules, which are supposed to have an effect on neuromediation systems. Method - Our review is based on studies, which have been published during the past twenty years. For many studies, data are limited to adolescents and adults. So we expanded our review to data available in children. The data bases that we have used are medline and psyclit. Keywords have been chosen according to: pharmacological considerations (psychotropic, psychoactive drugs, psychopharmacology) and clinical symptoms (autism, automutilations, aggressive behavior, and hyperactivity). Hypothesis of a dysfunction in the neuromediation systems in autism - Many studies exist about biochemical abnormalities in

This review summarises the findings and applications from neuroimagingstudies in dementia with Lewy bodies (DLB), highlighting key differences between DLB and other subtypes of dementia. We also discuss the increasingly important role of imaging biomarkers in differential diagnosis and outline promising areas for future research in DLB. DLB shares common clinical, neuropsychological and pathological features with Parkinson's disease dementia and other dementia subtypes, such as Alzheimer's disease. Despite the development of consensus diagnostic criteria, the sensitivity for differential diagnosis of DLB in clinical practice remains low and many DLB patients will be misdiagnosed. The importance of developing accurate imaging markers in dementia is highlighted by the potential for treatments targeting specific molecular abnormalities as well as the responsiveness to cholinesterase inhibitors and marked neuroleptic sensitivity of DLB. We review various brain imaging techniques that have been applied to investigate DLB, including the characteristic nigrostriatal degeneration in DLB using positron emission tomography (PET) and single-photon emission computed tomography (SPECT) tracers. Dopamine transporter loss has proven to reliably differentiate DLB from other dementias and has been incorporated into the revised clinical diagnostic criteria for DLB. To date, this remains the 'gold standard' for diagnostic imaging of DLB. Regional cerebral blood flow, 18 F-fluorodeoxygluclose-PET and SPECT have also identified marked deficits in the occipital regions with relative sparing of the medial temporal lobe when compared to Alzheimer's disease. In addition, structural, diffusion, and functional magnetic resonance imaging techniques have shown alterations in structure, white matter integrity, and functional activity in DLB. We argue that the multimodal identification of DLB-specific biomarkers has the potential to improve ante-mortem diagnosis and contribute to our

The application of neuroimaging methods to product marketing - neuromarketing - has recently gained considerable popularity. We propose that there are two main reasons for this trend. First, the possibility that neuroimaging will become cheaper and faster than other marketing methods; and second, the hope that neuroimaging will provide marketers with information that is not obtainable through conventional marketing methods. Although neuroimaging is unlikely to be cheaper than other tools in the near future, there is growing evidence that it may provide hidden information about the consumer experience. The most promising application of neuroimaging methods to marketing may come before a product is even released - when it is just an idea being developed.

This study created a database of pediatric age-specific MRI brain templates for normalization and segmentation. Participants included children from 4.5 through 19.5 years, totaling 823 scans from 494 subjects. Open-source processing programs (FSL, SPM, ANTS) constructed head, brain and segmentation templates in 6 month intervals. The tissue classification (WM, GM, CSF) showed changes over age similar to previous reports. A volumetric analysis of age-related changes in WM and GM based on these templates showed expected increase/decrease pattern in GM and an increase in WM over the sampled ages. This database is available for use for neuroimagingstudies (blindedforreview). PMID:22799759

The neuroanatomical correlates of human sexual desire, arousal, and behavior have been characterized in recent years with functional brain imaging techniques such as magnetic resonance imaging (MRI) and positron emission tomography (PET). Here, we briefly review the results of functional neuroimagingstudies in humans, whether healthy or suffering from sexual disorders, and the current models of regional and network activation in sexual arousal. Attention is paid, in particular, to findings from both regional and network studies in the past 3 years. We also identify yet unanswered and pressing questions of interest to areas of ongoing investigations for psychiatric, scientific, and forensic disciplines.

A quantitative, coordinate-based meta-analysis combined data from 354 participants across 22 fMRI studies and one positron emission tomography (PET) study to identify the differences in neural correlates of figurative and literal language processing, and to investigate the role of the right hemisphere (RH) in figurative language processing.…

A systematic review of 208 studies comprising functional magnetic resonance imaging and diffusion tensor imaging data in patients with "autism spectrum disorder" (ASD) was conducted, in order to determine whether these data support the forthcoming DSM-5 proposal of a social communication and behavioral symptom dyad. Studies consistently reported…

The introduction of neuroscientific evidence in criminal trials has given rise to fears that neuroimagery presented by an expert witness might inordinately influence jurors' evaluations of the defendant. In this experiment, a diverse sample of 1,170 community members from throughout the U.S. evaluated a written mock trial in which psychological, neuropsychological, neuroscientific, and neuroimage-based expert evidence was presented in support of a not guilty by reason of insanity (NGRI) defense. No evidence of an independent influence of neuroimagery was found. Overall, neuroscience-based evidence was found to be more persuasive than psychological and anecdotal family history evidence. These effects were consistent across different insanity standards. Despite the non-influence of neuroimagery, however, jurors who were not provided with a neuroimage indicated that they believed neuroimagery would have been the most helpful kind of evidence in their evaluations of the defendant.

Contradictory views are expressed in the literature about the role played by serendipity in discoveries that led to modern psychopharmacology. This article attempts to resolve these contradictions by providing an operational definition of serendipity. The utility of the proposed definition is explored in the context of 18 discoveries. The results show that the most common pattern in the development of early psychiatric medications is serendipitous observation leading to non-serendipitous demonstration of clinical utility. The analysis also reveals examples of relatively pure serendipitous and non-serendipitous discoveries. The proposed definition appears to be reliable and valid.

One of the essential tasks of neuropsychoanalysis is to investigate the neural correlates of sexual drives. Here, we consider the four defining characteristics of sexual drives as delineated by Freud: their pressure, aim, object, and source. We systematically examine the relations between these characteristics and the four-component neurophenomenological model that we have proposed based on functional neuroimagingstudies, which comprises a cognitive, a motivational, an emotional and an autonomic/neuroendocrine component. Functional neuroimagingstudies of sexual arousal (SA) have thrown a new light on the four fundamental characteristics of sexual drives by identifying their potential neural correlates. While these studies are essentially consistent with the Freudian model of drives, the main difference emerging between the functional neuroimaging perspective on sexual drives and the Freudian theory relates to the source of drives. From a functional neuroimaging perspective, sources of sexual drives, conceived by psychoanalysis as processes of excitation occurring in a peripheral organ, do not seem, at least in adult subjects, to be an essential part of the determinants of SA. It is rather the central processing of visual or genital stimuli that gives to these stimuli their sexually arousing and sexually pleasurable character. Finally, based on functional neuroimaging results, some possible improvements to the psychoanalytic theory of sexual drives are suggested. PMID:24672467

Neuroimaging techniques such as functional magnetic resonance imaging and positron emission tomography have provided an unprecedented neurobiological perspective for research on personality traits. Evidence from task-related neuroimaging has shown that extraversion is associated with activations in regions of the anterior cingulate cortex, dorsolateral prefrontal cortex, middle temporal gyrus and the amygdala. Currently, resting-state neuroimaging is being widely used in cognitive neuroscience. Initial exploration of extraversion has revealed correlations with the medial prefrontal cortex, anterior cingulate cortex, insular cortex, and the precuneus. Recent research work has indicated that the long-range temporal dependence of the resting-state spontaneous oscillation has high test-retest reliability. Moreover, the long-range temporal dependence of the resting-state networks is highly correlated with personality traits, and this can be used for the prediction of extraversion. As the long-range temporal dependence reflects real-time information updating in individuals, this method may provide a new approach to research on personality traits.

For over a century, scientists have sought to see through the protective shield of the human skull and into the living brain. Today, an array of technologies allows researchers and clinicians to create astonishingly detailed images of our brain's structure as well as colorful depictions of the electrical and physiological changes that occur within it when we see, hear, think and feel. These technologies-and the images they generate-are an increasingly important tool in medicine and science. Given the role that neuroimaging technologies now play in biomedical research, both neuroscientists and nonexperts should aim to be as clear as possible about how neuroimages are made and what they can-and cannot-tell us. Add to this that neuroimages have begun to be used in courtrooms at both the determination of guilt and sentencing stages, that they are being employed by marketers to refine advertisements and develop new products, that they are being sold to consumers for the diagnosis of mental disorders and for the detection of lies, and that they are being employed in arguments about the nature (or absence) of powerful concepts like free will and personhood, and the need for citizens to have a basic understanding of how this technology works and what it can and cannot tell us becomes even more pressing.

Advances in structural and functional neuroimaging have occurred at a rapid pace over the past two decades. Novel techniques for measuring cerebral blood flow, metabolism, white matter connectivity, and neural network activation have great potential to improve the accuracy of diagnosis and prognosis for patients with traumatic brain injury (TBI), while also providing biomarkers to guide the development of new therapies. Several of these advanced imaging modalities are currently being implemented into clinical practice, whereas others require further development and validation. Ultimately, for advanced neuroimaging techniques to reach their full potential and improve clinical care for the many civilians and military personnel affected by TBI, it is critical for clinicians to understand the applications and methodological limitations of each technique. In this review, we examine recent advances in structural and functional neuroimaging and the potential applications of these techniques to the clinical care of patients with TBI. We also discuss pitfalls and confounders that should be considered when interpreting data from each technique. Finally, given the vast amounts of advanced imaging data that will soon be available to clinicians, we discuss strategies for optimizing data integration, visualization and interpretation. PMID:23361483

A systematic review of 208 studies comprising functional magnetic resonance imaging and diffusion tensor imaging data in patients with 'autism spectrum disorder' (ASD) was conducted, in order to determine whether these data support the forthcoming DSM-5 proposal of a social communication and behavioral symptom dyad. Studies consistently reported abnormal function and structure of fronto-temporal and limbic networks with social and pragmatic language deficits, of temporo-parieto-occipital networks with syntactic-semantic language deficits, and of fronto-striato-cerebellar networks with repetitive behaviors and restricted interests in ASD patients. Therefore, this review partially supports the DSM-5 proposal for the ASD dyad.

The British Association for Psychopharmacology guidelines specify the scope and targets of treatment for bipolar disorder. The third version is based explicitly on the available evidence and presented, like previous Clinical Practice Guidelines, as recommendations to aid clinical decision making for practitioners: it may also serve as a source of information for patients and carers, and assist audit. The recommendations are presented together with a more detailed review of the corresponding evidence. A consensus meeting, involving experts in bipolar disorder and its treatment, reviewed key areas and considered the strength of evidence and clinical implications. The guidelines were drawn up after extensive feedback from these participants. The best evidence from randomized controlled trials and, where available, observational studies employing quasi-experimental designs was used to evaluate treatment options. The strength of recommendations has been described using the GRADE approach. The guidelines cover the diagnosis of bipolar disorder, clinical management, and strategies for the use of medicines: in short-term treatment of episodes, relapse prevention and stopping treatment. The use of medication is integrated with a coherent approach to psychoeducation and behaviour change. PMID:26979387

A quantitative, coordinate-based meta-analysis combined data from 354 participants across 22 fMRI studies and one positron emission tomography (PET) study to identify the differences in neural correlates of figurative and literal language processing, and to investigate the role of the right hemisphere (RH) in figurative language processing. Studies that reported peak activations in standard space contrasting figurative vs. literal language processing at whole brain level in healthy adults were included. The left and right IFG, large parts of the left temporal lobe, the bilateral medial frontal gyri (medFG) and an area around the left amygdala emerged for figurative language processing across studies. Conditions requiring exclusively literal language processing did not activate any selective regions in most of the cases, but if so they activated the cuneus/precuneus, right MFG and the right IPL. No general RH advantage for metaphor processing could be found. On the contrary, significant clusters of activation for metaphor conditions were mostly lateralized to the left hemisphere (LH). Subgroup comparisons between experiments on metaphors, idioms, and irony/sarcasm revealed shared activations in left frontotemporal regions for idiom and metaphor processing. Irony/sarcasm processing was correlated with activations in midline structures such as the medFG, ACC and cuneus/precuneus. To test the graded salience hypothesis (GSH, Giora, 1997), novel metaphors were contrasted against conventional metaphors. In line with the GSH, RH involvement was found for novel metaphors only. Here we show that more analytic, semantic processes are involved in metaphor comprehension, whereas irony/sarcasm comprehension involves theory of mind processes.

The purpose of our study was to identify and characterize the 100 most-cited articles in neuroimaging. Based on the database of Journal Citation Reports, we selected 669 journals that were considered as potential outlets for neuroimaging articles. The Web of Science search tools were used to identify the 100 most-cited articles relevant to neuroimaging within the selected journals. The following information was recorded for each article: publication year, journal, category and impact factor of journal, number of citations, number of annual citations, authorship, department, institution, country, article type, imaging technique used, and topic. The 100 most-cited articles in neuroimaging were published between 1980 and 2012, with 1995-2004 producing 69 articles. Citations ranged from 4384 to 673 and annual citations ranged from 313.1 to 24.9. The majority of articles were published in radiology/imaging journals (n=75), originated in the United States (n=58), were original articles (n=63), used MRI as imaging modality (n=85), and dealt with imaging technique (n=45). The Oxford Centre for Functional Magnetic Resonance Imaging of the Brain at John Radcliffe Hospital (n=10) was the leading institutions and Karl J. Friston (n=11) was the most prolific author. Our study presents a detailed list and an analysis of the 100 most-cited articles in the field of neuroimaging, which provides an insight into historical developments and allows for recognition of the important advances in this field.

For the purpose of developing multiple, complementary, fully labeled electronic brain atlases and an atlas-based neuroimaging system for analysis, quantification, and real-time manipulation of cerebral structures in two and three dimensions, we have digitized, enhanced, segmented, and labeled the following print brain atlases: Co-Planar Stereotaxic Atlas of the Human Brain by Talairach and Tournoux, Atlas for Stereotaxy of the Human Brain by Schaltenbrand and Wahren, Referentially Oriented Cerebral MRI Anatomy by Talairach and Tournoux, and Atlas of the Cerebral Sulci by Ono, Kubik, and Abernathey. Three-dimensional extensions of these atlases have been developed as well. All two- and three-dimensional atlases are mutually preregistered and may be interactively registered with an actual patient's data. An atlas-based neuroimaging system has been developed that provides support for reformatting, registration, visualization, navigation, image processing, and quantification of clinical data. The anatomical index contains about 1,000 structures and over 400 sulcal patterns. Several new applications of the brain atlas database also have been developed, supported by various technologies such as virtual reality, the Internet, and electronic publishing. Fusion of information from multiple atlases assists the user in comprehensively understanding brain structures and identifying and quantifying anatomical regions in clinical data. The multiple brain atlas database and atlas-based neuroimaging system have substantial potential impact in stereotactic neurosurgery and radiotherapy by assisting in visualization and real-time manipulation in three dimensions of anatomical structures, in quantitative neuroradiology by allowing interactive analysis of clinical data, in three-dimensional neuroeducation, and in brain function studies.

Neuroimaging offers a powerful means to assess the trajectory of brain degeneration in a variety of disorders, including Alzheimer's disease (AD). Here we describe how multi-modal imaging can be used to study the changing brain during the different stages of AD. We integrate findings from a range of studies using magnetic resonance imaging (MRI), positron emission tomography (PET), functional MRI (fMRI) and diffusion weighted imaging (DWI). Neuroimaging reveals how risk genes for degenerative disorders affect the brain, including several recently discovered genetic variants that may disrupt brain connectivity. We review some recent neuroimagingstudies of genetic polymorphisms associated with increased risk for late-onset Alzheimer's disease (LOAD). Some genetic variants that increase risk for drug addiction may overlap with those associated with degenerative brain disorders. These common associations offer new insight into mechanisms underlying neurodegeneration and addictive behaviors, and may offer new leads for treating them before severe and irreversible neurological symptoms appear.

Over the last four decades, a range of different neuroimaging tools have been used to study human auditory attention, spanning from classic event-related potential studies using electroencephalography to modern multimodal imaging approaches (e.g., combining anatomical information based on magnetic resonance imaging with magneto- and electroencephalography). This review begins by exploring the different strengths and limitations inherent to different neuroimaging methods, and then outlines some common behavioral paradigms that have been adopted to study auditory attention. We argue that in order to design a neuroimaging experiment that produces interpretable, unambiguous results, the experimenter must not only have a deep appreciation of the imaging technique employed, but also a sophisticated understanding of perception and behavior. Only with the proper caveats in mind can one begin to infer how the cortex supports a human in solving the “cocktail party” problem. PMID:23850664

In this study we investigated sensorimotor processing of painful pressure stimulation on the lower back of patients with chronic lower back pain (CLBP) by using functional near-infrared spectroscopy (fNIRS) to measure changes in cerebral hemodynamics and oxygenation. The main objectives were whether patients with CLBP show different relative changes in oxy- and deoxyhemoglobin ([O2Hb] and [HHb]) in the supplementary motor area (SMA) and primary somatosensory cortex (S1) compared to healthy controls (HC). Twelve patients with CLBP (32 ± 6.1 years; range: 24–44 years; nine women) and 20 HCs (33.5 ± 10.7 years; range 22–61 years; eight women) participated in the study. Painful and non-painful pressure stimulation was exerted with a thumb grip perpendicularly to the spinous process of the lumbar spine. A force sensor was attached at the spinous process in order to control pressure forces. Tactile stimulation was realized by a one-finger brushing. Hemodynamic changes in the SMA and S1 were measured bilaterally using a multi-channel continuous wave fNIRS imaging system and a multi-distant probe array. Patients with CLBP showed significant stimulus-evoked hemodynamic responses in [O2Hb] only in the right S1, while the HC exhibited significant [O2Hb] changes bilaterally in both, SMA and S1. However, the group comparisons revealed no significant different hemodynamic responses in [O2Hb] and [HHb] in the SMA and S1 after both pressure stimulations. This non-significant result might be driven by the high inter-subject variability of hemodynamic responses that has been observed within the patients group. In conclusion, we could not find different stimulus-evoked hemodynamic responses in patients with CLBP compared to HCs. This indicates that neither S1 nor the SMA show a specificity for CLBP during pressure stimulation on the lower back. However, the results point to a potential subgrouping regarding task-related cortical activity within the CLBP group; a finding worth

In this study we investigated sensorimotor processing of painful pressure stimulation on the lower back of patients with chronic lower back pain (CLBP) by using functional near-infrared spectroscopy (fNIRS) to measure changes in cerebral hemodynamics and oxygenation. The main objectives were whether patients with CLBP show different relative changes in oxy- and deoxyhemoglobin ([O2Hb] and [HHb]) in the supplementary motor area (SMA) and primary somatosensory cortex (S1) compared to healthy controls (HC). Twelve patients with CLBP (32 ± 6.1 years; range: 24-44 years; nine women) and 20 HCs (33.5 ± 10.7 years; range 22-61 years; eight women) participated in the study. Painful and non-painful pressure stimulation was exerted with a thumb grip perpendicularly to the spinous process of the lumbar spine. A force sensor was attached at the spinous process in order to control pressure forces. Tactile stimulation was realized by a one-finger brushing. Hemodynamic changes in the SMA and S1 were measured bilaterally using a multi-channel continuous wave fNIRS imaging system and a multi-distant probe array. Patients with CLBP showed significant stimulus-evoked hemodynamic responses in [O2Hb] only in the right S1, while the HC exhibited significant [O2Hb] changes bilaterally in both, SMA and S1. However, the group comparisons revealed no significant different hemodynamic responses in [O2Hb] and [HHb] in the SMA and S1 after both pressure stimulations. This non-significant result might be driven by the high inter-subject variability of hemodynamic responses that has been observed within the patients group. In conclusion, we could not find different stimulus-evoked hemodynamic responses in patients with CLBP compared to HCs. This indicates that neither S1 nor the SMA show a specificity for CLBP during pressure stimulation on the lower back. However, the results point to a potential subgrouping regarding task-related cortical activity within the CLBP group; a finding worth

Tensor-based morphometry can recover three-dimensional longitudinal brain changes over time by nonlinearly registering baseline to follow-up MRI scans of the same subject. Here, we compared the anatomical distribution of longitudinal brain structural changes, over 12 months, using a subset of the ADNI dataset consisting of 20 patients with Alzheimer's disease (AD), 40 healthy elderly controls, and 40 individuals with mild cognitive impairment (MCI). Each individual longitudinal change map (Jacobian map) was created using an unbiased registration technique, and spatially normalized to a geometrically-centered average image based on healthy controls. Voxelwise statistical analyses revealed regional differences in atrophy rates, and these differences were correlated with clinical measures and biomarkers. Consistent with prior studies, we detected widespread cerebral atrophy in AD, and a more restricted atrophic pattern in MCI. In MCI, temporal lobe atrophy rates were correlated with changes in mini-mental state exam (MMSE) scores, clinical dementia rating (CDR), and logical/verbal learning memory scores. In AD, temporal atrophy rates were correlated with several biomarker indices, including a higher CSF level of p-tau protein, and a greater CSF tau/beta amyloid 1-42 (ABeta42) ratio. Temporal lobe atrophy was significantly faster in MCI subjects who converted to AD than in non-converters. Serial MRI scans can therefore be analyzed with nonlinear image registration to relate ongoing neurodegeneration to a variety of pathological biomarkers, cognitive changes, and conversion from MCI to AD, tracking disease progression in 3-dimensional detail.

Understanding the human neuro-anatomy of face recognition is a long-standing goal of Cognitive Neuroscience. Studies of patients with face recognition impairment following brain damage (i.e., acquired prosopagnosia) have revealed the specificity of face recognition, the importance and nature of holistic/configural perception of individual faces, and the distribution of this function in the ventral occipito-temporal (VOT) cortex, with a right hemispheric dominance. Yet, neuroimagingstudies in this field have essentially focused on a single face-selective area of the VOT and underestimated the right hemisphere superiority. Findings in these studies have also been taken as supporting a hierarchical view of face perception, according to which a face is decomposed into parts in early face-selective areas, these parts being subsequently integrated into a whole representation in higher-order areas. This review takes a historical and current perspective on the study of acquired prosopagnosia and neuroimaging that challenges this latter view. It argues for a combination of these methods, an approach suggesting a coarse-to-fine emergence of the holistic face percept in a non-hierarchical network of cortical face-selective areas.

Ayahuasca, a South American psychotropic plant tea obtained from Banisteriopsis caapi and Psychotria viridis, combines monoamine oxidase-inhibiting beta-carboline alkaloids with N,N-dimethyltryptamine (DMT), a psychedelic agent showing 5-HT(2A) agonist activity. In a clinical research setting, ayahuasca has demonstrated a combined stimulatory and psychedelic effect profile, as measured by subjective effect self-assessment instruments and dose-dependent changes in spontaneous brain electrical activity, which parallel the time course of subjective effects. In the present study, the spatial distribution of ayahuasca-induced changes in brain electrical activity was investigated by means of low-resolution electromagnetic tomography (LORETA). Electroencephalography recordings were obtained from 18 volunteers after the administration of a dose of encapsulated freeze-dried ayahuasca containing 0.85 mg DMT/kg body weight and placebo. The intracerebral power density distribution was computed with LORETA from spectrally analyzed data, and subjective effects were measured by means of the Hallucinogen Rating Scale (HRS). Statistically significant differences compared to placebo were observed for LORETA power 60 and 90 min after dosing, together with increases in all six scales of the HRS. Ayahuasca decreased power density in the alpha-2, delta, theta and beta-1 frequency bands. Power decreases in the delta, alpha-2 and beta-1 bands were found predominantly over the temporo-parieto-occipital junction, whereas theta power was reduced in the temporomedial cortex and in frontomedial regions. The present results suggest the involvement of unimodal and heteromodal association cortex and limbic structures in the psychological effects elicited by ayahuasca.

Objective To report radiological findings observed in computed tomography (CT) and magnetic resonance imaging (MRI) scans of the first cases of congenital infection and microcephaly presumably associated with the Zika virus in the current Brazilian epidemic. Design Retrospective study with a case series. Setting Association for Assistance of Disabled Children (AACD), Pernambuco state, Brazil. Participants 23 children with a diagnosis of congenital infection presumably associated with the Zika virus during the Brazilian microcephaly epidemic. Main outcome measures Types of abnormalities and the radiological pattern of lesions identified on CT and MRI brain scans. Results Six of the 23 children tested positive for IgM antibodies to Zika virus in cerebrospinal fluid. The other 17 children met the protocol criteria for congenital infection presumably associated with the Zika virus, even without being tested for IgM antibodies to the virus—the test was not yet available on a routine basis. Of the 23 children, 15 underwent CT, seven underwent both CT and MRI, and one underwent MRI. Of the 22 children who underwent CT, all had calcifications in the junction between cortical and subcortical white matter, 21 (95%) had malformations of cortical development, 20 (91%) had a decreased brain volume, 19 (86%) had ventriculomegaly, and 11 (50%) had hypoplasia of the cerebellum or brainstem. Of the eight children who underwent MRI, all had calcifications in the junction between cortical and subcortical white matter, malformations of cortical development occurring predominantly in the frontal lobes, and ventriculomegaly. Seven of the eight (88%) children had enlarged cisterna magna, seven (88%) delayed myelination, and six each (75%) a moderate to severe decrease in brain volume, simplified gyral pattern, and abnormalities of the corpus callosum (38% hypogenesis and 38% hypoplasia). Malformations were symmetrical in 75% of the cases. Conclusion Severe cerebral damage was

This article is an update of the algorithm for schizophrenia from the Psychopharmacology Algorithm Project at the Harvard South Shore Program. A literature review was conducted focusing on new data since the last published version (1999-2001). The first-line treatment recommendation for new-onset schizophrenia is with amisulpride, aripiprazole, risperidone, or ziprasidone for four to six weeks. In some settings the trial could be shorter, considering that evidence of clear improvement with antipsychotics usually occurs within the first two weeks. If the trial of the first antipsychotic cannot be completed due to intolerance, try another until one of the four is tolerated and given an adequate trial. There should be evidence of bioavailability. If the response to this adequate trial is unsatisfactory, try a second monotherapy. If the response to this second adequate trial is also unsatisfactory, and if at least one of the first two trials was with risperidone, olanzapine, or a first-generation (typical) antipsychotic, then clozapine is recommended for the third trial. If neither trial was with any these three options, a third trial prior to clozapine should occur, using one of those three. If the response to monotherapy with clozapine (with dose adjusted by using plasma levels) is unsatisfactory, consider adding risperidone, lamotrigine, or ECT. Beyond that point, there is little solid evidence to support further psychopharmacological treatment choices, though we do review possible options.

Background Disasters are mega-scale catastrophic events which cause trauma and mental health sequelae. A review of early pharmacological interventions for the prevention of psychiatric disorders following disasters is sorely needed. Methods A literature search of “Psychiatric Sequelae AND Disasters”, “Disaster mental health/Disaster psychiatry”, “Psychotropics AND Disasters”, and “Drug therapy AND Disasters” yielded 213 articles, 38 of which were included in the review. Results Common post-disaster psychiatric conditions are: posttraumatic stress disorder (PTSD), depressive and anxiety disorders, substance use disorders and medically-unexplained psychological symptoms. Early psychopharmacological interventions to prevent PTSD provide promising evidence for hydrocortisone in medically ill trauma populations. Less robust benefits were noted for other pharmacological interventions. No reported trials have explored prevention of depression or other common post-disaster psychiatric conditions. Conclusion Hydrocortisone shows promise in preventing and reducing the psychiatric sequelae of PTSD following disasters. Further evaluation of hydrocortisone and other potentially beneficial psychopharmacological interventions are needed. PMID:28138200

Advances in neuroimaging have helped illuminate our understanding of how the brain works in the presence of chronic pain, which often persists with unknown etiology or after the painful stimulus has been removed and any wounds have healed. Neuroimaging has enabled us to make great progress in identifying many of the neural mechanisms that contribute to chronic pain, and to pinpoint the specific regions of the brain that are activated in the presence of chronic pain. It has provided us with a new perception of the nature of chronic pain in general, leading researchers to move toward a whole-brain approach to the study and treatment of chronic pain, and to develop novel technologies and analysis techniques, with real potential for developing new diagnostics and more effective therapies. We review the use of neuroimaging in the study of chronic pain, with particular emphasis on magnetic resonance imaging. PMID:28163658

This review integrates cognitive, socioemotional, and neuroimaging perspectives on self-development. Neural correlates of key processes implicated in personal and social identity are reported from studies of children, adolescents, and adults, including autobiographical memory, direct and reflected self-appraisals, and social exclusion. While cortical midline structures of medial prefrontal cortex and medial posterior parietal cortex are consistently identified in neuroimagingstudies considering personal identity from a primarily cognitive perspective ("who am I?"), additional regions are implicated by studies considering personal and social identity from a more socioemotional perspective ("what do others think about me, where do I fit in?"), especially in child or adolescent samples. The involvement of these additional regions (including tempo-parietal junction and posterior superior temporal sulcus, temporal poles, anterior insula, ventral striatum, anterior cingulate cortex, middle cingulate cortex, and ventrolateral prefrontal cortex) suggests mentalizing, emotion, and emotion regulation are central to self-development. In addition, these regions appear to function atypically during personal and social identity tasks in autism and depression, exhibiting a broad pattern of hypoactivation and hyperactivation, respectively.

Evidence from lesion and cortical-slice studies implicate the neocortical cholinergic system in the modulation of sensory, attentional and memory processing. In this review we consider findings from sixty-three healthy human cholinergic functional neuroimagingstudies that probe interactions of cholinergic drugs with brain activation profiles, and relate these to contemporary neurobiological models. Consistent patterns that emerge are: (1) the direction of cholinergic modulation of sensory cortex activations depends upon top-down influences; (2) cholinergic hyperstimulation reduces top-down selective modulation of sensory cortices; (3) cholinergic hyperstimulation interacts with task-specific frontoparietal activations according to one of several patterns, including: suppression of parietal-mediated reorienting; decreasing ‘effort’-associated activations in prefrontal regions; and deactivation of a ‘resting-state network’ in medial cortex, with reciprocal recruitment of dorsolateral frontoparietal regions during performance-challenging conditions; (4) encoding-related activations in both neocortical and hippocampal regions are disrupted by cholinergic blockade, or enhanced with cholinergic stimulation, while the opposite profile is observed during retrieval; (5) many examples exist of an ‘inverted-U shaped’ pattern of cholinergic influences by which the direction of functional neural activation (and performance) depends upon both task (e.g. relative difficulty) and subject (e.g. age) factors. Overall, human cholinergic functional neuroimagingstudies both corroborate and extend physiological accounts of cholinergic function arising from other experimental contexts, while providing mechanistic insights into cholinergic-acting drugs and their potential clinical applications. PMID:21708219

Recent functional neuroimagingstudies have investigated brain activity patterns during sleep in humans, beyond the conventionally defined sleep stages. These works have characterized the neural activations related to the major brain oscillations of sleep, that is, spindles and slow waves during non-rapid-eye-movement sleep and ponto-geniculo-occipital waves during rapid-eye-movement sleep. These phasic events have been found associated with increases of brain activity in specific neural networks, which identify structures involved in the generation of sleep oscillations. Most importantly, these results confirm that, even during the deepest stages of sleep, neuronal network activities are sustained and organized by spontaneous brain oscillations of sleep. The understanding of the neural mechanisms underlying sleep oscillations is fundamental since increasing evidence suggests a pivotal role for these rhythms in the functional properties of sleep. In particular, interactions between the sleeping brain and the surrounding environment are closely modulated by neuronal oscillations of sleep. Functional neuroimagingstudies have demonstrated that spindles distort the transmission of auditory information to the cortex, therefore isolating the brain from external disturbances during sleep. In contrast, slow waves evoked by acoustic stimulation--and also termed K-complexes--are associated with larger auditory cortex activation, thus reflecting an enhanced processing of external information during sleep. Future brain imaging studies of sleep should further explore the contribution of neuronal oscillations to the off-line consolidation of memory during sleep.

Functional magnetic resonance imaging (fMRI) is the workhorse of imaging-based human cognitive neuroscience. The use of fMRI is ever-increasing; within the last 4 years more fMRI studies have been published than in the previous 17 years. This large body of research has mainly focused on the functional localization of condition- or stimulus-dependent changes in the blood-oxygenation-level dependent signal. In recent years, however, many aspects of the commonly practiced analysis frameworks and methodologies have been critically reassessed. Here we summarize these critiques, providing an overview of the major conceptual and practical deficiencies in widely used brain-mapping approaches, and exemplify some of these issues by the use of imaging data and simulations. In particular, we discuss the inherent pitfalls and shortcomings of methodologies for statistical parametric mapping. Our critique emphasizes recent reports of excessively high numbers of both false positive and false negative findings in fMRI brain mapping. We outline our view regarding the broader scientific implications of these methodological considerations and briefly discuss possible solutions. PMID:25071503

Functional neuroimaging and neuropsychological performance indicate a prefrontal dysfunction in schizophrenia patients. Frontal morphological brain abnormalities are also evident in these patients, but the relationship between neuropsychology and neuroimaging findings remains unclear. In this study, thirty patients with schizophrenia and 30 control participants were assessed using a neuropsychological test battery sensitive to fronto-striatal system dysfunction. Computed tomography (CT) scans were used to calculate the distance from the corpus callosum to the frontal pole corrected for brain size (anterioposterior length) in the group of patients and in a group of control participants with negative radiological findings. Schizophrenia patients performed significantly worse than controls in all frontal lobe tests. Corrected length from the corpus callosum to the frontal pole was reduced in patients with schizophrenia. This easy-to-perform measurement has not been used in previous studies, and indicates that schizophrenia patients have structural frontal abnormalities. However, correlations between structural and functional measures fail to show a clear relationship between the prefrontal performance and the main CT measures. As a rule, the trend observed in the correlation matrix pointed towards a relationship between CT parameters and a dysfunction on neuropsychological tests sensitive to frontal lobe damage.

Multimodal non-invasive neuroimaging in rodents constitutes an attractive tool for studying neurobiological processes in vivo. At present, imaging studies of brain anatomy and function as well as the investigation of structure-function relationships belong to the standard repertoire of neuroscientists. Molecular imaging adds a new perspective. The mapping of the receptor distribution and receptor occupancy can nowadays be complemented by specific readouts of receptor function either by visualizing the activity of signaling pathways or mapping the physiological consequences of receptor stimulation. Molecular information is obtained through the use of imaging probes that combine a target-specific ligand with a reporter moiety that generates a signal that can be detected from outside the body. For imaging probes targeting the central nervous system, penetration of the intact blood-brain barrier constitutes a major hurdle. Molecular imaging generates specific information and therefore has a large potential for disease phenotyping (diagnostics), therapy development and monitoring of treatment response. Molecular imaging is still in its infancy and major developments in imaging technology, probe design and data analysis are required in order to make an impact. Rodent molecular neuroimaging will play an important role in the development of these tools.

Over the last quarter century, researchers have peered into the living human brain to develop and refine mechanistic accounts of alcohol-induced behavior, as well as neurobiological mechanisms for development and maintenance of addiction. These in vivo neuroimagingstudies generally show that acute alcohol administration affects brain structures implicated in motivation and behavior control, and that chronic intoxication is correlated with structural and functional abnormalities in these same structures, where some elements of these decrements normalize with extended sobriety. In this review, we will summarize recent findings about acute human brain responses to alcohol using neuroimaging techniques, and how they might explain behavioral effects of alcohol intoxication. We then briefly address how chronic alcohol intoxication (as inferred from cross-sectional differences between various drinking populations and controls) may yield individual brain differences between drinking subjects that may confound interpretation of acute alcohol administration effects. This article is part of the Special Issue Section entitled 'Neuroimaging in Neuropharmacology'.

The Extensible Neuroimaging Archive Toolkit (XNAT) is a software platform designed to facilitate common management and productivity tasks for neuroimaging and associated data. In particular, XNAT enables qualitycontrol procedures and provides secure access to and storage of data. XNAT follows a threetiered architecture that includes a data archive, user interface, and middleware engine. Data can be entered into the archive as XML or through data entry forms. Newly added data are stored in a virtual quarantine until an authorized user has validated it. XNAT subsequently maintains a history profile to track all changes made to the managed data. User access to the archive is provided by a secure web application. The web application provides a number of quality control and productivity features, including data entry forms, data-type-specific searches, searches that combine across data types, detailed reports, and listings of experimental data, upload/download tools, access to standard laboratory workflows, and administration and security tools. XNAT also includes an online image viewer that supports a number of common neuroimaging formats, including DICOM and Analyze. The viewer can be extended to support additional formats and to generate custom displays. By managing data with XNAT, laboratories are prepared to better maintain the long-term integrity of their data, to explore emergent relations across data types, and to share their data with the broader neuroimaging community.

Noninvasive functional neuroimaging, as an important tool for basic neuroscience research and clinical diagnosis, continues to face the need of improving the spatial and temporal resolution. While existing neuroimaging modalities might approach their limits in imaging capability mostly due to fundamental as well as technical reasons, it becomes increasingly attractive to integrate multiple complementary modalities in an attempt to significantly enhance the spatiotemporal resolution that cannot be achieved by any modality individually. Electrophysiological and hemodynamic/metabolic signals reflect distinct but closely coupled aspects of the underlying neural activity. Combining fMRI and EEG/MEG data allows us to study brain function from different perspectives. In this review, we start with an overview of the physiological origins of EEG/MEG and fMRI, as well as their fundamental biophysics and imaging principles; it is followed by a review of major progresses in understanding and modeling the neurovascular coupling, methodologies for the fMRI-EEG/MEG integration and EEG-fMRI simultaneous recording; finally, important remaining issues and perspectives (including brain connectivity imaging) are summarized. PMID:20634915

Specific phobia is an anxiety disorder characterized by irrational fear and avoidance of specific things or situations, interfering significantly with the patients' daily life. Treatment for the disorder consists of both pharmacological and psychological approaches, mainly cognitive behavioral therapy (CBT). Neuroimaging techniques have been used in an attempt to improve our understanding of the neurobiology of SP and of the effects of treatment options available. This review describes the design and results of eight articles investigating the neuroimaging correlates of pharmacological and psychological treatments for SP. The studies show that CBT is effective in SP, leading to a reduction of anxiety symptoms that is accompanied by functional alterations in the brain. The results of pharmacological interventions for SP are less uniform, but suggest that the partial agonist of the NMDA (N-methyl D-aspartate) receptor DCS (D-cycloserine) can be used in combination with psychotherapy techniques for the achievement of quicker treatment response and that DCS modulates the function of structures implicated in the neurobiology of SP. Further research should explore the augmentation of CBT treatment with DCS in controlled trials.

Medulloblastomas are the most common malignant childhood brain tumors arising in the posterior fossa. Treatment improvements for these tumors have meant that there are a greater number of survivors, but this long-term patient survival has increased the awareness of resulting neurocognitive deficits. Impairments in attention, memory, executive functions, and intelligence quotient demonstrate that the cerebellum likely plays a significant role in numerous higher cognitive functions such as language, cognitive, and emotional functions. In addition, children with medulloblastoma not only have cerebellar lesions but also brain white matter damages due to radiation and chemotherapy. Functional neuroimaging, a noninvasive method with many advantages, has become the standard tool in clinical and cognitive neuroscience research. By reviewing functional neuroimagingstudies, this review aims to clarify the role of the cerebellum in cognitive function and explain